Hematoma in the cheek may develop if the needle passes through a vessel while it is introduced. Compression over the cheek by cold pack after the needle is withdrawn may be helpful. Misplacement of needles into incorrect skull base foramina can lead to vascular damage and secondary hypertension that, in turn, can lead to bleeding. In case of deep needle placement, one can enter the brain stem and cause hemorrhage. Inadvertent injection of therapeutic agents into this cul-de-sac can spread to other intracranial structures, producing profound and rapid loss of consciousness and collapse. This is obviously an eminently reversible situation when local anesthetic agents are used, but in the event that such a catastrophe occurred with neurolytic agents, inadvertent neurolysis of adjacent cranial nerves could occur. Irritation of the dura may cause persistent headache, and in some patients, nausea and vomiting lasting for days may also be observed. If blood is aspirated, the needle should be replaced, and if bleeding continues, the procedure should be stopped. The endpoint is reached when the desired division of the trigeminal nerve has become slightly analgesic but not anesthetic. Usually at about 70°C, analgesia occurs and further coagulations are made at the same temperature until some analgesia is produced in the required division. At this stage, the time for each coagulation can be increased or decreased; however, if the temperature is increased without first trying extra time, anesthesia will suddenly develop. Sequential throbbing of the cannula may occasionally be observed during the early seconds of the lesion. To prevent hematoma in the cheek, ice compression after the needle is withdrawn should be done in every instance. Weakness of the homolateral masseter muscle may occur during the postoperative period. Because of the subsequent analgesia of the conjunctiva, the eye must be protected from chronic inflammatory processes that would go undetected because of the altered sensation. Therefore, it is usually necessary to approximate the upper and lower eyelids surgically to reduce the area of conjunctiva exposed to dust and other environmental sources of contamination. Protective spectacles with side shields can also help reduce the introduction of foreign bodies into the numb eye. Another difficulty with long-term hemifacial analgesia is saliva dribbling from the anesthetized half of the mouth; this can sometimes be alleviated by an antisialagogue such as diphenhydramine, 25 mg tid. Shorter duration of pain relief, higher recurrence rates, and development of fibrosis at the foramen ovale are the main disadvantages. Slight sensory deficit and Somatic Blocks 87 moderate rate of recurrence may be the advantages of gasserian ganglion compression. However, it cannot be connected to a single branch, and the gauge of the needle entering the foramen ovale is larger than the ones used in other percutaneous methods, which may damage the nerve. In another study, technical failure for glycerol was reported to be as high as 15%. Pain Recurrence Evaluating pain recurrence is not easy because of the heterogeneity of the follow-up reported. The highest rate of recurrence is 54% for glycerol rhizotomy, with a mean follow-up of 4 years. Fibrosis may develop at the entrance of foramen ovale, enhancing further injections. All these techniques are less morbid and more cost effective than open surgical techniques. However, each technique must be applied in precise indications and in well-equipped centers with experienced personnel. Comparison of Techniques In conclusion, the initial success rate with all three approaches is similar-91­93%. A number of transient cranial nerve deficits were also seen with a 2% chance of permanent ipsilateral hearing loss. However, much more frequently the indications are chronic, debilitating painful conditions. Clearly, the use of fluoroscopy and additional training led to better outcome and reduction of potentially devastating complications. All three percutaneous techniques may be used to block the trigeminal nerve in the treatment of neuralgic pain of the face. An orbital approach described originally by Rudolph Matas involves inserting a needle through the orbital cavity and exiting the infraorbital fissure. The more commonly used lateral approach described by Levy and Baudoin31 in 1906 is described and preferred by the authors. The maxillary artery and five terminal branches are also contained within the pterygopalatine fossa. The main part of the maxillary nerve, which constitutes the second division of the trigeminal nerve, can be anesthetized in the pterygopalatine fossa. It provides excellent postoperative pain relief for such surgical maneuvers, and it is also used to treat chronic pain, most frequently for diagnostic and therapeutic blocks involving painful tumors of the maxillary antrum that are unresponsive to more conventional methods. The nerve innervates the maxillary sinus, as well as the anterior teeth of the upper jaw via the anterior and middle superior alveolar nerves. The branch that leaves the infraorbital foramen innervates the skin of the face, the underlying mucosa from the lower eyelid to the upper lip. While the nerve is at the pterygopalatine fossa, it is connected to the pterygopalatine ganglion, through which it gives the branches to the nasal cavity, pharynx, and palate. The zygomatic branch supplies the lateral portion of the face and posterior superior alveolar branch supplies the upper molar region. The branches of the maxillary nerve are divided into four regional groups: (1) the intracranial group, including the middle meningeal nerve, which innervates the dura mater of the medial cranial fossa; (2) the pterygopalatine group including zygomatic nerve, which provides sensory innervation to the temporal and lateral zygomatic region, and sphenopalatine branches to innervate the mucosa of the maxillary sinus, upper gums, upper molars, and mucous membranes of the cheek; (3) the infraorbital canal group, comprising the anterosuperior alveolar branch innervating the incisors and canines, the anterior wall of the maxillary antrum, the floor of the nasal cavity, and the middle superior branch, supplying the premolars; and (4) the infraorbital facial group, consisting of the inferior palpebral branch, which innervates the conjunctiva and the skin of the lower eyelid, the external nasal branch, which supplies the side of the nose, and the superior labial branch, which supplies the skin of the upper lip and part of oral mucosa. Mandibular notch between the condyle and coronoid process Extraoral Approach notch, which should be close to the middle of the zygoma. The needle is again advanced with the pterygopalatine fossa until a paresthesia is obtained. Three to 5 ml of local anesthetic is injected, although some authors advocate the use of as much as 10 ml. Once satisfactory placement is obtained, pulsed radiofrequency for 120­-180 seconds at 42°C for two cycles is performed. Intraoral Approach Three technique variations when performing intraoral maxillary block follow: 1. A retractor or left index finger retracts the cheek at the angle of the mouth upward and backwards until the first upper molar tooth is seen. The needle is introduced through the mucosa over the tooth and advanced backward, the mandibular notch is identified, which is most easily done by having the patient open and close the mouth. Initial needle direction (1) and redirection (2) after it encounters the pterygoid plate are shown. When the contact with the bone is lost at a depth of 3­4 cm from the point of entrance, the needle is then advanced 0. Pterygomaxillary approach: the needle is introduced from the back of the upper molar tooth, directed upward and inward, almost perpendicularly to the tooth. The needle passes laterally to the angle formed by the tuberosity of the maxilla and the pterygoid process at a depth of 3. Posterior palatinal approach: the same technique by the pterygomaxillary route is employed through the posterior palatinal foramen into the canal until the needle tip reaches the sphenomaxillary fossa, and 2 ml of 1% lidocaine is administered. Infraorbital Block the needle is directed upward and backward, and the entrance to the foramen is felt. The needle should not be introduced more than 1 cm and only a small amount of glycerol, 0. Complications the infraorbital nerve is the terminal branch of the maxillary nerve. In some cases with trigeminal neuralgia, in spite of radiofrequency lesioning or other percutaneous techniques of the gasserian ganglion, the pain in the area of innervation of the infraorbital nerve continues and infraorbital block may be useful at that instance. The infraorbital canal is directed 45 degrees backward and upward and 20­25 degrees outward and varies from 1 to 1. As soon as there is contact with maxilla, below the foramen, In the extraoral approach, it is essential that the needle be introduced in a horizontal fashion, and it certainly should not enter the pterygomaxillary fissure in a cephalad direction or advance too deeply, because anesthetic injections here are rapidly spread to the posterior aspect of the orbit and the optic nerve, producing temporary blindness with reversible agents or, more seriously, permanent blindness with neurolytic agents. Because of the exceedingly vascular nature of the compartment in which the maxillary nerve lies (the pterygomaxillary fissure is a veritable network of small vessels), intravascular injection is quite possible, and meticulous aspiration tests are essential. If the direction of the needle is too backwards, penetration to the pharnyx is possible. The close proximity of the orbit to this nerve makes it likely to be involved in a complication. Orbital swelling, anesthesia of the orbital tissues, ophthalmoplegia, loss of visual acuity, or diplopia can occur if the local anesthetic or neurolytic solution enters the infraorbital fissure. Damage to vascular structures can cause hemorrhage into the orbit, and blindness can occur. An intravascular injection can also occur despite negative aspiration if the maxillary or mandibular artery or vein is injured during the performance of the block. Aspiration of air usually indicates that the needle has been placed too far posteriorly and the pharynx has been entered. However, when the tip of the needle contacts with the lateral pterygoid lamina, the patient perceives this as a paresthesia. The paresthesia should be felt in the whole area; where the nerve innervates, the pain of the periosteum is more localized. The sensory fibers arise from the anterolateral portion of the gasserian ganglion, whereas the motor fibers are the same motor nerve mentioned in connection with the trigeminal ganglion, which arises from the pons and passes beneath the gasserian ganglion to reach the foramen ovale, through which, together with the sensory root, it leaves the cranial cavity. Within or immediately outside the foramen ovale, the two roots fuse into a single trunk. It followed soon after the first description of the trigeminal ganglion block was described. Soon after it is formed, the mandibular nerve gives off two small branches: the nervus spinosus, which enters the cranial cavity with the middle meningeal artery to supply the dura, and the nerve to the internal pterygoid muscle. The small anterior trunk, which is composed mostly of motor fibers, then promptly divides into the masseteric, the anterior and posterior deep temporal, and the external pterygoid nerves that supply the muscles of mastication and also give off a small sensory branch, the buccinator, which supplies the mucous membrane and skin over this muscle. The large posterior trunk, on the other hand, is composed mostly of sensory fibers. After a short course it also divides into the auriculotemporal, the lingual, and inferior alveolar nerves. The auriculotemporal nerve arises from the posterior aspect of this trunk and immediately runs posterolaterally beneath the external pterygoid muscle to reach the medial side of the neck of the mandible, where it turns sharply cephalad to ascend between the anterior border of the auricle and the condyle of the mandible under cover of the parotid gland, finally reaching the subcutaneous tissue overlying the zygomatic arch, where it divides into the anterior auricular, the external meatal, articular, parotid, and superficial temporal branches. The terminal branch of the inferior alveolar nerve is the mental nerve, which exits the mandible via the mental foramen and provides sensory innervation to the chin and to the skin and mucous membrane of the lower lip. It is also useful for chronic pain states, such as carcinoma of the tongue, lower jaw, or floor of the mouth. For best results, paresthesia should be elicited before 2 to 4 ml of anesthetic solution is injected. Intraoral Approach the cheek is retracted by the index finger or retractor until the second upper molar tooth is seen. After the pterygoid plate is touched, the needle is slightly withdrawn and pushed posterior until it slips off the pterygoid plate. The direction of the needle from lateral view should be toward the midpoint of the zygomatic arch and from the frontal view toward the outer canthus. At a depth of 4­5 cm, the needle will contact the infratemporal plate, and at that area paresthesia should be sought. As the needle is walked posteriorly off the lateral pterygoid plate, it comes to lie on the superior constrictor muscle of the pharynx, which is attached to the border of the lateral pterygoid plate. If the tip of the needle enters the pharynx, air bubbles will be seen during aspiration. A very close posterolateral relation of the mandibular nerve at this site is the middle meningeal artery, which enters the cranial cavity through the spinous foramen, thus making meticulous aspiration tests necessary. Hemorrhage in the cheek often occurs during and following the block by the anterolateral extraoral route. If paresthesia is not obtained at this depth, the needle should be withdrawn and the landmarks reconsidered before it is reintroduced. In some cases in spite of blocking the gasserian ganglion, the peripheric branches of the trigeminal nerve are blocked. Also, in some cases with trigeminal neuralgia, only the mental nerve is affected and mental nerve block may be adequate. A line is drawn from the two lower bicuspid teeth perpendicular to the lower margin of the mandible. The distance between the gingival margin of mandible and lower margin of the mandible is bisected. Through this bisecting point a line is drawn parallel to the lower margin of the mandible. These two lines cross each other at right angles and their intersection marks the position of the mental foramen. The quadrant in which the second bicuspid lies is bisected and a point is taken on the bisector. The needle should not be introduced too deep in the foramen and the solution should be given in very few amounts in order to prevent compression over the nerve, which may cause neuropathy. Intracranial section of the glossopharyngeal nerve was first performed by Adson in 1925 and was subsequently refined by Dandy.

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• Loxapine
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Remarkably, there was a gradual improvement in pain and by the 6th week the patient was pain free. The patient was weaned off of all analgesics except gabapentin, and this pain relief lasted for 6 months. Pulsed radiofrequency lesioning was repeated, and the patient reported complete pain relief at 8 months. Treatments for glossopharyngeal neuralgia can be divided into surgical versus nonsurgical. Several classes of drugs are used empirically with anecdotal success: carbamazepine, phenytoin, diazepam, amitriptyline, phenobarbital, ketamine, and baclofen. We are aware of one death due to iatrogenic vascular injury following styloidectomy. Percutaneous radiofrequency thermocoagulation of the glossopharyngeal nerve has been successful in treating primary and secondary glossopharyngeal neuralgia. Technically, there are several percutaneous methods to target the glossopharyngeal nerve. An intraoral approach is often used for preemptive analgesia,67 but this method caries the risk of infection and iatrogenic injury to several neurovascular structures, including internal carotid artery, vagus nerve, brainstem, vertebral artery, and upper cervical spinal nerves. This approach, however, can cause severe damage to the vital neurovascular structures mentioned earlier. Sloughing of skin and subcutaneous tissue has been associated with anesthesia dolorosa. The glossopharyngeal nerve is susceptible to trauma from needle, hematoma, or compression during injection procedures. Such complications, although usually transitory, can be quite upsetting for the patient. Even though risk of infection is uncommon, it is ever present, especially in patients with cancer who are immunocompromised. This makes identification of the styloid process much easier, since this particular bony landmark is now almost subcutaneous, allowing this block to be performed easily. Because of the proximity of the large vascular conduits of the internal carotid artery and the internal jugular vein, the risks of intravascular injection are always significant, demanding meticulous aspiration tests. With the temporary and perhaps permanent analgesia produced by this block, a degree of incoordination of swallowing, with the accompanying potential risk of aspiration, must be appreciate d by patients and attendants alike. With numbness of half of the pharynx and the larynx, ingestion and swallowing are often severely compromised. Even small amounts of local anesthetic injected into the carotid artery at this site can produce profound local anesthetic toxicity. Both these complications may be well tolerated by patients with terminal cancer pain. The major complications associated with glossopharyngeal nerve block are related to trauma to the internal jugular vein and carotid artery. Blockade of the motor portion of the glossopharyngeal nerve can result in dysphagia secondary to weakness of the stylopharyngeus muscle. Reflex tachycardia secondary to vagal nerve block is also observed in some patients. The greater occipital nerve ascends in the posterior neck over the dorsal surface of the rectus capitis posterior major muscle, at the midpoint of this muscle; turns dorsally to pierce the semispinalis capitis; and then runs a short distance rostrolaterally, lying deep to the trapezius. The nerve becomes superficial below the superior nuchal line, along with the occipital artery. It supplies the medial portion of the posterior scalp as far anterior as the vertex. The lesser occipital nerve passes superiorly along the posterior border of the sternocleidomastoid muscle, innervating the lateral portion of the posterior scalp and the cranial surface of the pinna of the ear. There are three landmarks for locating the greater occipital nerve: (1) the occipital artery, (2) the mastoid process, and (3) the greater occipital protuberance. An imaginary line is passed through these landmarks, and the occipital artery is generally found at a point approximately one-third the distance from the occipital protuberance on the superior nuchal line. The artery is palpated and a short (1­1/2-inch), 25-gauge needle is inserted through the skin at the level of the superior nuchal line. The needle is advanced until a paresthesia or bone is encountered and then withdrawn 2 mm. If the artery is not identified, the medication is injected in a fan-like fashion (medially and laterally) and 5 ml of local anesthetic is injected. The lesser occipital nerve is blocked by introducing the needle medial to the origin of the sternocleidomastoid muscle at the mastoid process. The needle is aimed in a cephalad and medial direction until it contacts the skull. The needle is withdrawn 2 mm and aspirated, after which approximately 3 ml of local anesthetic should be injected. When the paresthesia is met, 1 ml 6% phenol in glycerine or Omnipaque is slowly injected after negative aspiration. If a diagnostic block is planned, the dose should be limited to 1­2 ml to minimize confusion Lesser occipital nerve A 5-cm radiofrequency needle with 5-mm active tip is advanced to make contact, through a previously introduced catheter, with the bone in the close vicinity of the nerve. Due to the high vascularity of the scalp, ecchymosis or hematoma formation can occur. Nerve injury due to the direct trauma from the needle or compression of nerves with large volume of local anesthetic can occur. If the needle is introduced too deeply when trying to achieve paresthesia, inadvertent placement of the needle into the foramen magnum can occur. Administration of local anesthetics in this situation can result in total spinal block and respiratory depression. Somatic Blocks 103 with relief of myofascial pain when larger volumes are injected. The vascularity and the proximity to the arterial supply give rise to an increased incidence of postblock ecchymosis and hematoma formation. These complications can be decreased if manual pressure is applied to the area of the block immediately after the injection. Application of cold packs for 20-minute periods after the block will also decrease the amount of postprocedure pain and bleeding. Strict care must be taken to avoid inadvertent needle placement into the foramen magnum, as the subarachnoid administration of local anesthetic in this region will result in an immediate total spinal block. Following review of literature and anatomy, the entrapment of the greater occipital nerve in the suboccipital compartment was assumed. Ten milliliters of local anesthetic and steroid mixtures were injected from just below the nuchal line bilaterally, through the deep fascia trapezius and semispinalis muscle layers into the suboccipital compartment. The technique of the procedure, virtually unchanged, was repeated several thousand times in numerous cases in subsequent years. In a 1994 presentation in Perth, Australia, Umberto Rossi, in a patient with the same condition, dissected down to the C1-C2 lamina to cut the inferior oblique muscle with prompt relief of the pain on recovery. He also observed that while the pain would stop, these patients would develop similar pain on the opposite side. The suboccipital compartmental injection technique from the beginning has been a bilateral injection. In 2004, similar neurosurgical observations were made where the sectioning of the inferior oblique muscle was recommended. From the clinical experience of many users, a pattern of problems has become evident. The injection technique coming from just below the nuchal line through the facial layers is clearly a very safe technique; however, if the tip of a sharp needle enters the greater occipital nerve, retrograde longitudinal spread may give rise to a "locked-in phenomenon" where the patient stops breathing and stares with dilated pupils. One of the patients had this occurrence; after approximately 30 minutes of ventilation, the patient made a full and uneventful recovery. A similar event occurred in the practice of one of the trainees after 6­8 years of practice and many procedures with similar good outcomes. Several cases of infarction of the brain stem were reported in which glossopharyngeal nerve impairment and swallowing difficulty were the consequences as predicted by Seelander. Lessons learned are that it is a bilateral disease and repeat injections are safe and effective. It originates from the transverse process of the atlas and inserts on the occipital bone between the superior and inferior nuchal lines lateral to the semispinalis capitus. The obliquus capitus inferior is the lateral boundary below, and it originates from the spinous process of the axis and inserts on the transverse process of the atlas. The roof of the space is a tough layer of connective tissue beneath the semispinalis capitus, and the floor is the occipito-atlantal membrane and posterior arch of the atlas. The posterior branch of the first occipital nerve, the suboccipital nerve, exits posteriorly between the occiput and the posterior arch of the atlas. It supplies the muscles bounding the suboccipital triangle and communicates with the greater and lesser occipital nerves. Burchiel K: Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. Wilkinson H: Trigeminal nerve peripheral branch phenol/glycerol injections for tic douloureux. Schlosser H: Erfahrungen in der Neuralgiebehandlung mit Alkoholeinspritzungen: Verhandl. Harris W: Persistent pain in lesions of the peripheral and central nervous system. Cushing H: the role of deep alcohol injections in the treatments of trigeminal neuralgia. Hartel F: Die Leitungsanesthesie und Injektionsbehandlung des Ganglion Gasseri und der Trigeminusaeste. Hakanson S: Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Mullan S, Lichtor T: Percutaneous microcompression of the trigeminal ganglion for trigeminal neuralgia. Brisman R: Analgesia and sedation during percutaneous radiofrequency electrocoagulation for trigeminal neuralgia. Broggi G, Franzini A, Lasio G, et al: Long-term results of percutaneous retrogasserian thermorhizotomy for "essential" trigeminal neuralgia. Burchiel K, Steege T, Howe J, Loeser J: Comparison of percutaneous radiofrequency gangliolysis and microvascular decompression for the surgical management of tic douloureux. Fraoili B, Esposito V, Guidetti B, et al: Treatment of trigeminal neuralgia by thermocoagulation, glycerolization, and percutaneous compression of gasserian ganglion and/or retrogasserian rootlets: long-term results and therapeutic protocol. Fujimaki T, Fukushima T, Miyazaki S: Percutaneous retrogasserian glycerol injection in the management of trigeminal neuralgia: longterm follow-up results. Moretti R, Torre P, Antonello B, et al: Gabapentin treatment of glossopharyngeal neuralgia: a follow-up of four years of a single case. Resnick D, Janetta P, Bissonnette D, et al: Microvascular decompression for glossopharyngeal neuralgia. Patel A, Kassam A, Horowitz M, et al: Microvascular decompression in the management of glossopharyngeal neuralgia: analysis of 217 cases. Kondo A: Follow-up results using microvascular decompression for treatment of glossopharyngeal neuralgia. Arias M: Percutaneous radio-frequency thermocoagulation with low temperature in the treatment of essential glossopharyngeal neuralgia. Arbit E, Kro G: Percutaneous radiofrequency neurolysis guided by computed tomography for the treatment of glossopharyngeal neuralgia. Giorgi C, Broggi G: Surgical treatment of glossopharyngeal neuralgia and pain from cancer of the nasopharynx-a 20 year experience. Van Zundert J, Raj P, Erdine S, et al: Application of radiofrequency treatment in practical pain management: state of the art. Giannoni C, White S, Enneking F, et al: Ropivacaine with or without clonidine improves pediatric tonsillectomy pain. Becser N, Bovim G, Sjaastad O: Extramural nerves in the posterior part of the head. Gille O, Lavignolle B, Vital J: Surgical treatment of greater occipital neuralgia by neurolysis of the greater occipital nerve and sectioning of the inferior oblique muscle. Rossi P, Di Lorenzo G, Faroni J, et al: Seasonal, extratrigeminal, episodic paroxysmal hemicrania successfully treated with single suboccipital steroid injections. Ambrosini A, Vandenheede M, Rossi P, et al: Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study. It lies in the pterygopalatine fossa, which is approximately 1 cm wide and 2 cm high, and resembles a "vase" on a lateral fluoroscopic view. The pterygopalatine fossa is bordered anteriorly by the posterior wall of the maxillary sinus, posteriorly by the medial plate of the pterygoid process, and medially by the perpendicular plate of the palatine bone and superiorly by the sphenoid sinus, and laterally it communicates with the infratemporal fossa. The ganglion within the fossa is located posterior to the middle turbinate of the nose and lies a few millimeters deep to the lateral nasal mucosa. It is "suspended" from the maxillary branch of the trigeminal nerve at the pterygopalatine fossa via the pterygopalatine nerves, and lies medial to the maxillary branch when viewed in the sagittal plane. Posteriorly, it is connected to the vidian nerve, also known as the nerve of the pterygoid canal, which is formed by the greater petrosal and the deep petrosal nerves. The ganglion itself has efferent branches and forms the superior posterior lateral nasal and pharyngeal nerves. Caudally, the ganglion is in direct connection with the greater and lesser palatine nerves. The sympathetic component begins with preganglionic sympathetic fibers originating in the upper thoracic spinal cord, forming the white rami communicantes, and coursing through the sympathetic ganglion, where the preganglionic fibers synapse with the postganglionic ones. The postganglionic fibers then join the carotid nerves before branching off and traveling through the deep petrosal and vidian nerves. The indications supported by current literature include sphenopalatine and trigeminal neuralgia, cluster and migraine headaches, and atypical facial pain.

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The first thoracic ganglion is fused with the lower cervical ganglion to help make up the stellate ganglion. As the chain moves caudad, it changes its position, the upper thoracic ganglia lying just beneath the rib and the lower thoracic ganglia moving farther anterior to rest along the posterolateral surface of the vertebral body. Given the proximity of the thoracic somatic nerves to the thoracic sympathetic chain, the potential exists for both neural pathways to be blocked during blockade of the thoracic sympathetic ganglion. This led them to study the location of T2 and T3 sympathetic ganglia in 24 freshly embalmed adult cadavers. In the dorsoventral location, the T2 ganglia on the right side had a median location of 19 mm (range 12­31 mm) dorsal to the ventral surface of the vertebral body, and the left side had a median location of 17 mm (range 6­27 mm) dorsal to the ventral surface. The rightsided T3 median location was 20 mm (range 9­31 mm) dorsal to the ventral surface of T3 vertebral body. The relationship of the ganglia caudad and cephalad to the vertebral bodies was more constant. The median location of the T2 ganglia was 2-mm rostral to the midpoint of the T2 vertebral body on the right side (range 1­7 mm), between the head of the ribs. For practical purposes, this is equivalent to the posterior third of the thoracic vertebrae in the lateral view. Here, they ascend cephalad and synapse with postganglionic fibers, primarily in T2, but also in T3, in the stellate ganglia, and in the middle cervical ganglia. By blocking T2 and T3, which are the "key" synaptic stations, all the synaptic nerves destined for the upper limbs can be blocked. Neurolytic block of the sympathetic chain from T2 to T8 can be used in patients with severe intractable pain caused by cancer of the esophagus, heart, bronchi, trachea, lung, pleura, or by some other chronic pathologic process of the upper two-thirds of the esophagus. Destruction of this chain is indicated for palliation of pain syndromes that have responded to thoracic sympathetic blockade with local anesthetics. Patients should be evaluated with respect to any anatomical distortions of the thorax prior to surgery. The fluoroscope is then used to identify the T2 vertebral body in an anteroposterior view. The fluoroscope is then obliqued approximately 20 degrees toward the ipsilateral side. The fluoroscope is then rotated in a cephalocaudad direction approximately 20 degrees. A 16-gauge, 2-inch angiocatheter is advanced toward the lateral border at T2 above the third rib, in a tunnel view, with the aid of fluoroscopy. The lateral stippling demonstrates the rotation of the fluoroscope to create a tunneled view for radiographic needle placement. The dye spread is up and down the thoracic vertebral column, and unilateral placement is confirmed if the spread follows the dome of the lung, the needle is more lateral than the parietal pleura. If this is a diagnostic block, local anesthetic and steroid solutions are injected. This volume is generally sufficient to block both the T2 and T3 sympathetic ganglia. This can be confirmed by watching the spread of dye before and after injection of local anesthetic. Fentanyl, midazolam, and lidocaine all produce vasodilation and affect sympathetic function for hours after the procedure. Radiofrequency Thermocoagulation of T2 and T3 Sympathetic Ganglion the needle is advanced, hugging the lateral edge of the T2 vertebral body. Stimulation at 50 Hz and 2 V is used to record any stimulation of intercostal nerves. Prior to lesioning and after stimulation, local anesthetic and steroids are injected. The curved blunt needle is shown in a "tunnel" view at the T2 vertebral level (arrow). The needle tip is at the midpoint to the posterior third of the thoracic vertebral body. The contrast medium is seen over the vertebral body (arrow) without tracking of the contrast into the neuroforamina. When lesioning is complete, the needle hub is directed in a medialcaudad direction. A chest radiograph is ordered to rule out pneumothorax, and the pain and temperature are rechecked. The patient is advised of late-occurring pneumothorax, and instructed that if he or she has increased shortness of breath or chest pain, to go to the emergency room for evaluation. This too can be minimized by meticulously performing sensory and motor stimulation prior to lesioning. If no dysesthesias or muscle contractions occur in the somatic nerve (intercostal) distribution, then one could deduce that the needle tip is at least 1 cm away from the nerve root. The data of the incidence of neuritis by this procedure are still scant and need to be further evaluated. Staying within 4 cm of the spinous process is another safety factor that contributes to the success of the technique and alleviates pneumothoraces. The two radiofrequency needles can be seen in place at the T2 and T3 vertebral levels. The arrow indicates the correct position of the needle tip on the T2 andT3 sympathetic chain. A T4 block was done in eight of the blocks, T1 in one block, and T4 and T9 in another. It was not realized at the time the radiograph was read by the anesthesiologist, but was confirmed by the radiologist at a later time. The second pneumothorax occurred in a patient with deafferentation pain in the right upper extremity. The technique for splanchnic nerve block differs little from the classic retrocrural approach to the celiac plexus, except that the needles are aimed more cephalad in order to ultimately rest at the anterolateral margin of the T12 vertebral body. Abram and Boas26 described a technique for splanchnic nerve block that used a paravertebral transthoracic approach. The needle was advanced to rest against the anterolateral aspect of the T11 vertebral body. In the Boas technique, the needles are bilaterally advanced 6 cm lateral to the midline of T11 intercostal space contacting vertebral body. The predictable relationship of the splanchnic nerves to other structures allows for accurate needle placement and hence a low risk of iatrogenic damage. Other authors had different results in the application of splanchnic nerve blockades via various methods. The great splanchnic nerves run paravertebrally through the thorax, crus of the diaphragm and enter the abdominal cavity ending in the celiac ganglion. The lesser splanchnic nerves pass parallel to the great splanchnic nerves and end in the celiac ganglion. Abram and Boas26 have determined that the volume of this compartment is approximately 10 ml on each side. The recognition that splanchnic nerve block may provide relief of pain in a subset of patients who fail to obtain relief from celiac plexus block, has led to a renewed interest in this technique. Recently splanchnic nerve/nerves blockades have been applied solely or in conjunction with celiac blockade in patients with malignant or benign upper abdominal pain. All patients should have an intravenous catheter inserted in a large vein and securely anchored. Sedation is used to relax the patient on an as needed basis, taking into account the physical status of the patient. The patient needs to be kept awake and should be able to answer reliably during the testing of sensory and motor stimulation. The position on the table should be such that the C-arm could 262 Thorax both levels is at the junction of the rib and vertebra. With the oblique fluoroscopic view still in place, a 14-gauge, 5-cm extracath is inserted, such that the catheter traverses toward the target as a pinhead. When two-thirds of the extracath is inserted, the stylet is removed and the radiofrequency needle is inserted. In the lateral view, the needle is advanced until it reaches the junction of anterior one third and posterior two-thirds of the lateral aspect of the vertebral body, then aspirated for fluid, which could be blood, cerebrospinal fluid. Site of Needle Entry In the prone position, the T12 vertebral body is identified in the posteroanterior view of the fluoroscope. If the diaphragm shadows T12 vertebra and its rib, then the T11 rib is identified. The point of entry for Smaller volumes (12 to 15 ml) of absolute alcohol are recommended for single-needle procedures. Mixtures of 10% phenol and iodinated contrast medium (iohexol) remain stable for up to 3 months. The apparent greater affinity of phenol for vascular rather than neurologic tissue also represents a theoretic disadvantage, in view of the vascularity of the region surrounding the celiac plexus and splanchnic nerves. It is important to note that comparative studies between alcohol and phenol are not available. To approach this region, a curved 15-cm needle with a 15-mm lesion tip is recommended. The needle should remain retrocrural and posterior to the descending aorta; hence, safely away from the aorta. Then the tip can be turned medially once it reaches the lateral surface of the vertebral body. This ensures the needle remains medial to the interpleural surface and in close contact with the vertebral body. Watch for spread and dispersion of contrast material, especially in a blood vessel. A lateral view ensures that the needle stays posterior to the aorta and anterior to the foramen. Steroids help in treating the occasional occurrence of neuritis by reducing edema and inflammation of the lesioned structures. If the procedure is for the bilateral neurolysis, then the same procedure of testing and lesioning is done on the opposite site. The skin is draped sterilely, and the site of puncture is infiltrated with lidocaine 2%. On the left, the best trajectory is chosen to avoid organ perforation and to place the tip of the needle in the left retrocrural area. Two milliliters of contrast medium is injected through both needles to confirm the proper spread. Half a milliliter of nonionic contrast medium is applied, and, after controlling the position of the contrast medium, 20 ml of neurolytic solution is injected (1 ml contrast, 12 ml alcohol 96%, and 6 ml of lidocaine 0. The patient was placed in the prone position with a pillow beneath the chest/abdomen to facilitate opening of the interdiscal space. Next the fluoroscopy is placed in an oblique fashion and angled at 15­20 degrees or more for obtaining the best image of the disc to align the inferior endplates. After local anesthetic infiltration of the skin and the subcutaneous tissues with 2% lidocaine, a 22-gauge, 10-cm needle was introduced by tunnel vision lateral to the inferior aspect of the facet joint. The needle was then advanced further under lateral fluoroscopic control, and a 5-ml syringe with saline was attached for loss of resistance. When the needle passed outside the T11-T12 interdiscal space, 3 ml of contrast was administered to verify its final position. While further drawing back the needle, cephazolin 50 mg in 1 ml was administered to the disc to prevent discitis. One gram of cephazolin as a prophylactic antibiotic had been given intravenously 30 minutes before the procedure. It is important that patients should be re-evaluated with anteroposterior/lateral chest x-rays after the procedure to rule out pneumothorax. The risks of the splanchnic nerve block are similar to those of the celiac plexus block. Apart from the common risks associated with celiac and splanchnic nerve blocks, the rates of pneumothorax, thoracic duct injury, and inadvertent spread of the injected drug to the somatic nerve roots are higher for the splanchnic nerve block than for the celiac plexus block. Because of the close proximity of vital structures coupled with the use of large volumes of neurolytic drugs, side effects and complications may occur. Although the patient number is small, all the parameters associated with long-term debilitating chronic pain were improved. They found splanchnic nerve blockade with neurolytics superior to celiac plexus blockade on the basis of survival rates, quality of life, and side effects. Plancarte-Sánchez39 used percutaneous transdiscal splanchnic nerve blockade under tomographic control in 64 patients, aiming to reduce possible complications due to nerve blockade. Neither morbidity (which was minor) nor efficacy (70­80% immediate success and 60­75% persistence of effect until death) correlated with anatomic technique. Splanchnic nerve block maintains a deservedly meaningful role in the armamentarium of the contemporary pain specialist. Despite a dearth of scientifically determined outcome data, even the most critical observer is nearly certain to acknowledge the therapeutic value of these techniques in patients with viscerally mediated abdominal and/or back pain or neoplastic origin, especially early in the course of established disease. For patients with longer life expectancies, the role of celiac/splanchnic neural blockade is increasingly recognized as modest, on other than a diagnostic basis. Despite daunting logistic and ethical methodological barriers, there is a pressing need to design and undertake collaborative controlled trials aimed at better determining the relative value of various technical approaches. Plancarte-Sánchez R, Velazquez R, Patt R: Neurolytic blocks of the sympathetic axis. Garcia G: Percutaneous splanchnic nerve radiofrequency ablation for chronic abdominal pain. Phan P, Warneke C, Shah H, et al: Correlation of splanchnic nerve block efficacy and cancer staging. Kappis M: Sensibilitt und local ansthesie in chirurgischen gebiet der bauchhole mit besonderen bercksichtigung der splanchnichusansthesie. In Adriani J, editor: Nerve Blocks: A Manual of Regional Anesthesia for Practitioners of Medicine.

Usage: p.r.n.

Because liquid nitrogen is used to produce the freeze "burn" or lesion, the probes are typically bigger than can be used by the radiofrequency lesioning machines. However, they are a preferred choice in areas where the risk of neuritis is a concern. A timer is included for monitoring the time of the freeze and warming of the probe. Descriptions of the equipment for these techniques are provided in the following illustrations and legends. A link between cervical cancer and sexual contact was firmly established in 1842 by an Italian physician Rigoni-Stern, who analyzed death certificates of women in Verona during the period 1760­1839 and noted a high frequency of cervical cancer in married women, widows and prostitutes, but their rare occurrence in virgins and nuns (zur Hausen 2009). The first unequivocal demonstration of the contagious nature of genital warts did not arrive until 1907 when Ciuffo observed the transmission of warts using cell-free extracts (Martin and Gutkind 2008). Shope, a physician at the Rockefeller Institute for Medical Research, connected a virus to one of the most devastating diseases of the twentieth century-the influenza pandemic of 1918. In 1932, Shope learned of another disease of wild cottontails that produces long, hornlike growths on the head and face of the animal. He was able to isolate virus particles from tumors on captured animals and use cell-free extracts to inoculate domestic rabbits, which then developed similar tumors (Shope 1933). This observation led him to propose that the illness was virus-borne (Shope 1933). In 1934 and subsequent years, Rous and colleagues confirmed that the warts were benign tumors that had the potential to become cancerous (Rous and Beard 1934; Rous and Kidd 1938; Rous and Friedewald 1944). This was the first demonstration of the carcinogenic potential of rabbit papillomaviruses in cottontail and domestic rabbits. Despite clear indications of the causative roles of papillomaviruses in papilloma related diseases from different animal species, the exact mechanisms of the pathogenesis of papilloma diseases were nearly untouchable at the time. Subsequent studies had revealed the intratypic heterogeneity of plantar wart virus preparations (Gissmann and zur Hausen 1976) and type-specific endonuclease restriction patterns of various isolates (Gissmann et al. This clearly established the plurality of human papillomavirus types and paved the way to link specific papillomavirus types to cervical cancer. In 1972 zur Hausen and his research team initiated an attempt trying to establish a relationship between papillomavirus infections and cervical cancer. Based on anecdotal reports in the medical literature of rare malignant conversion of genital warts (condylomata acuminata) into squamous cell carcinomas (zur Hausen 1977), they noted that the epidemiological patterns of cervical cancer and condylomas were striking similar, which led them to hypothesize that cervical cancer may arise from infections with the virus found in condylomata acuminata (zur Hausen 1975, 1976; zur Hausen et al. In the late 1970s Meisels and Fortin postulated that koilocytotic cells found in cervical smears of patients with flat dysplastic lesions represent the cytopathogenic change of a papillomavirus infection (Meisels and Fortin 1976; Meisels et al. Initially they hypothesized that the detection of such koilocytotic cells permitted a differentiation between the koilocyte-positive "benign" proliferations and koilocyte-negative lesions, assumed to represent "truly premalignant" cells. It was upregulated E6 and E7 gene expression in cervical cancer that indicated their specific oncogenic roles. In the late 1980s cell transformation by these viral oncogenes was initially shown in rodent cells (Yasumoto et al. These findings were important for the initiation and understanding of intracellular events resulting in immortalization and eventually in a transformed phenotype of the viral genome harboring cells. This implied that viral gene expression was required for maintenance of the tumorigenic phenotype, and that E6 and E7 represented key viral oncogenes. What became clear from these analyses was that the papillomavirus reproductive cycle absolutely depends on complete squamous differentiation of the host epithelium and that squamous and glandular carcinomas do not support the productive program (Stoler and Broker 1986; Stoler et al. Viral activity is distinctly increased in lesions from patients with immunosuppressive disorders. In highgrade dysplasias and cancers, the viral genome is often integrated and only a subset of the viral genes is consistently expressed. Concurrently, the encoded viral proteins and their functions were identified using a variety of in situ and in vitro assays (Chow et al. Only when this portrait of viral activities and virus­host interactions in natural infections had emerged could development begin to establish appropriate experimental model systems that recapitulate real infections or selected elements of those infections. The vaccines have an excellent safety profile, are highly immunogenic, and have conferred complete type-specific protection against persistent infection and associated lesions in fully vaccinated women (Lowy and Schiller 2006). The development of prophylactic vaccines against human papillomavirus has been hailed as one of the most significant advances of recent years, which will dramatically reduce the mortality of human papillomavirus associated cancers. Viruses are mainly classified by phenotypic characteristics, such as morphology, nucleic acid type, mode of 6 J. The Baltimore classification (first defined in 1971) is a classification system based on genome types and replication strategies of viruses. According to the Baltimore classification system, viruses are divided into the following seven groups: I. The original Papovaviridae family was split into two families, Papillomaviridae and Polyomaviridae, nearly a decade ago. The only homologous segment shared by papilloma- and polyomaviruses is within the papillomavirus E1 genes and the polyomavirus T-antigens that correspond to a helicase, suggesting an ancient common origin of the replication proteins of these viruses (Clertant and Seif 1984; Rebrikov et al. Recently, two viruses of marsupials were published with a surprising genome organization: early genes resembling the polyomaviruses and late genes resembling the papillomaviruses (Woolford et al. These polyoma-papilloma "hybrid" viruses are more representative of a recombination event than of a shared common ancestor, and thus are not classified within the Papillomaviridae family (Bernard et al. Subtypes are defined by having homology differences of 2­10 %, whereas variants are defined as having homology differences of less than 2 % (de Villiers et al. High-risk types have the ability to induce squamous cell immortalization in vitro and can be detected in a subset of malignant neoplasms. Some Beta type papillomavirus are commensal agents, or agents which contribute or act together with another virus to cause lesions, since they are isolated many times from healthy skin or hair from humans or animals (Antonsson et al. Only three human members from this group are known, and all cause cutaneous papillomas in the general population (Doorbar 2005). The early promoter located upstream of the E6 gene is activated, and early viral proteins are expressed prior to productive replication (Longworth and Laimins 2004). Upon epithelial cell differentiation, the late promoter located in the E7 gene is activated, and the expression of L1 and L2 genes are induced (Hummel et al. The capsid is composed of two structural proteins, the major highly conserved protein L1 and the minor capsid protein L2 (Buck et al. E7 1000 E1 2000 E2 E4 3000 E5 4000 L2 5000 6000 L1 7000 Late poly A Early Late Promoter Early poly A. The core of the capsomeres is mainly composed of an antiparallel b-sandwich made up of eight b strands labeled B through I contribute. Viral capsids have evolved to fulfill numerous roles that are critical to the establishment of viral infection. After receptor engagement the virus is internalized and its coat is disassembled to allow the encapsulated genome access to the cellular transcription and replication machinery (Richards et al. Comparatively recent advances have allowed researchers to dissect the molecular workings and anatomy of this virus. Human tumor-associated viruses and new insights into the molecular mechanisms of cancer. A Virus-Induced Mammalian Growth with the Characters of a Tumor (the Shope Rabbit Papilloma): Iii. Crystalline virus-like particles from skin papillomas characterized by intranuclear inclusion bodies. Tumorigenic Nucleic Acid Extracts from Tissues of a Transplantable Carcinoma, Vx7. Electron microscopic detection of papilloma virus particles in selected koilocytotic cells in a routine cervical smear. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice. The causal link between human papillomavirus and invasive cervical cancer: a population-based case-control study in Colombia and Spain. Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. A novel virus detected in papillomas and carcinomas of the endangered western barred bandicoot (Perameles bougainville) exhibits genomic features of both the Papillomaviridae and Polyomaviridae. Genomic characterization of a novel virus found in papillomatous lesions from a southern brown bandicoot (Isoodon obesulus) in Western Australia. Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata. Phylogenetic classification of human papillomaviruses: correlation with clinical manifestations. Analysis of genomic sequences of 95 papillomavirus types: uniting typing, phylogeny, and taxonomy. Human papillomavirus type 13 and pygmy chimpanzee papillomavirus type 1: comparison of the genome organizations. Human papillomavirus and head and neck squamous cell carcinoma: recent evidence and clinical implications. Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck. Human papillomavirus infection as a prognostic factor in carcinomas of the oral cavity and oropharynx. Prevalence and type spectrum of human papillomaviruses in healthy skin samples collected in three continents. Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes. Structure of rabbit papilloma virus, with an appendix on the topography of contrast in negative-staining for electron-microscopy. Efficient self-assembly of human papillomavirus type 16L1 and L1-L2 into virus-like particles. Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein L1. Self-assembly of human papillomavirus type 1 capsids by expression of the L1 protein alone or by coexpression of the L1 and L2 capsid proteins. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus. Proteins Encoded by the Human Papillomavirus Genome and Their Functions Jiaping Xue, Benjamin J. E1 and E2 are viral replication proteins that play several roles during productive infection, while E4 proteins are thought to aide in virion release. E5, E6 and E7 are viral oncoproteins that are associated with the increased proliferation of suprabasal epithelial cells. By itself, E1 weakly binds to origin sequences, but this binding is enhanced through complex formation with E2 proteins (Dixon et al. A dimer of E1 and a dimer of E2 cooperatively bind to their adjacent sites with the N-terminal domain of E2 forming an interaction with the helicase domain of E1 (Sarafi and McBride 1995; Sedman et al. The full-length E2 protein is approximately 50 kDa in size and function as a dimers. The N terminus contains a transactivation domain that interacts with E1 helicase domain. The N-terminal domain of E1 contains both nuclear import and export signals that mediate E1 protein shuttling from the nucleus to the cytoplasm in a 20 J. E2 also anchors replicated viral episomes to mitotic chromosomes for correct segregation (You et al. In addition to its role in replication and genome segregation, the E2 protein is the major transcriptional regulator of the virus. The E1 and E2 proteins act as origin recognition factors (Longworth and Laimins 2004) and are essential in viral genome replication (Stubenrauch et al. High-risk E7 proteins by themselves cannot transform human keratinocytes, but together with E6, they can efficiently immortalize human keratinocytes (Munger et al. E7 interacts preferentially with the active, unphosphorylated, and E2F-bound form of pRb (Imai et al. This leads to the de-repression of E2F-responsive genes, whose expression is required for cell cycle progression from the G1 to the S phase. E2F6 is a pRb-independent, noncanonical member of the E2F transcription factor family which acts as a transcriptional repressor. E2F6 expression is activated in S phase in response to E2F activation, which represses E2F response genes and slows down S-phase progression and/or exit S-phase (Lyons et al. The suprabasal layers have exited the cell cycle and have begun the process of terminal differentiation (Pim and Banks 2010). During keratinocyte differentiation, loss of contact with the basal membrane is associated with increased levels of the Cyclin/Cdk inhibitors p21 and p27 (Missero et al. The major target of p21 and p27 in human keratinocytes is Cdk2, which is complexed with either Cyclin E or Cyclin A to drive the cell cycle from G1 to S phase and progression (Deshpande et al. The carboxy-termini of high-risk E7 proteins bind cyclin-dependent kinase inhibitors p21 and p27, efficiently neutralizing the inhibitory effects on cyclin E-and cyclin A-associated Cdk2 activities (Funk et al. This would allow the clonal outgrowth of cells that maintain a minimal level of telomerase activity, and is consistent with the notion that E6 plays a part in tumor progression by primarily promoting telomerase activity in high-grade cervical lesions and carcinomas (Moody and Laimins 2010). The function of the viral E6 protein complements that of E7 to prevent growth arrest or apoptosis induced by E7mediated cell-cycle entry in the upper epithelial layers. In addition to regulation of p53 activities, E6 also associates with Bak to inhibit apoptosis in a p53 independent manner. This role of E6 is of key significance in the development of cervical cancers, as its accumulation of secondary mutations go unchecked.