It has been reported that inflammation triggers the sprouting of Aβ afferents to substantia gelatinosa that originally terminate at deeper laminae. This sprouting could be mediated by a change occurring at the early state of inflammation. To elucidate mechanisms of the sprouting following inflammation in the spinal dorsal horn, blind patch-and in vivo patch-clamp recordings were made from substantia gelatinosa neurons of rats 2 days after inflammation. In vivo patch-clamp recordings showed an increase of spontaneous firing of afferents and elimination of accommodation that is a common property of non-nociceptive receptors. Consistently, the slice study demonstrated an increase of transmitter release that was mediated by newly synthesized BDNF. These changes occurring at the early state of inflammation would be an underlying mechanism that triggers the sprouting of Aβ afferents to substantia gelatinosa.

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Many types of animal pain models have been reported and each animal model has different physiological and pathological mechanisms that produce pain. For example, in some models, pain perception is enhanced mainly by the sensitization of the peripheral nerve. In other models, spinal sensitization is the most important mechanism for enhanced pain perception.
First, we have to understand the characteristics of each animal pain model. Then, we choose the animal models according to the goal of the study.

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Immunohistochemical approach in pain research is one of the effective methods to search for existence of some substance and investigate localization of receptors or neurotransmitters. Although immunohistochemical staining is widely used, the method sometimes brings confusion to those who are unfamiliar to it. Here we give comments on preparations of tissues and general procedures of immunohistochemical methods for beginner of pain research. Taking streptavidin-biotinylated peroxidase complex method as a case of enzyme labeled immunohistochemical stainings, we refer to practical arrangements of these procedures and important factors to be paid attentions to when the methods do not work well.

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We have been caring for patients with chronic peripheral artery diseases including thromboangiitis obliterans (TAO) and arteriosclerosis obliterans (ASO). From 1990-1999, 107 patients with chronic peripheral artery disease were admitted to the Department of Anesthesiology in Gunma University Hospital. The number of patients with TAO was 63, among which 15 patients underwent amputation of at least one of their extremities. The number of patients with ASO was 40, among which 15 had amputation. 84% of patients with TAO and 80% of those with ASO had a history of smoking. The smoking rate among patients who had amputation was 100% in the patients with TAO and 92% in those with ASO, respectively. The patients who had amputation had a significantly lower ankle brachial index, serum high density lipoprotein (HDL) concent-ration, and higher total cholesterol/HDL ratio compared to the patients who did not have amputation. Co-existing diseases in the patients included diabetes mellitus, hypertension, ischemic heart disease and brain infarction, regardless of whether or not they had a limb amputated. The medical treatments included anticoagulant drug therapy, vasodilator therapy, sympathetic ganglion block and hyperbaric oxygen therapy. It was suggested that, in order to prevent exacerbation of the disease and to avoid amputation, patients should stop smoking. Also, a strategy to prevent arteriosclerosis should be adopted. A novel therapy, autologous bone marrow transplantation, is considered to be promising as a fundamental therapy.

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Purpose: Nicotinic receptor agonists and muscarinic receptor agonists have been reported to produce antinociceptive effects. We hypothesized that acetylcholine receptor antagonists would decrease the pain threshold. The aim of the present study was to clarify this hypothesis with regard to drugs that are commonly used perioperatively: pancuronium, vecuronium, atropine, and scopolamine. Methods: Nociceptive effects of each drug were studied in ICR strain mice using hot-plate, acetic acid-writhing, and tail-pinch tests. Results: Hot-plate jumping latency was decreased by administration of pancuronium, but not by vecuronium. It was also decreased by higher doses of atropine and scopolamine. In the acetic acid-writhing test, four antagonists increased the frequency of writhing reactions. Conclusion: The present results suggest that antagonists of nicotinic and muscarinic receptors lower the pain threshold.

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We report a case of accidental subdural catheterization during continuous cervical epidural block. In a 56-year-old woman being treated for pain due to herpes zoster in the left C₆ area, an epidural catheter was inserted into the epidural space between the C₆ and C₇ vertebra. After confirmation that the cerebrospinal fluid did not flow backward, 1% mepivacaine was injected. Then, the systolic blood pressure decreased to 60-70mmHg, requiring administration of epinephrine, and the pain was eased. After the patient recovered from hypotension, administration of continuous epidural block with 1% mepivacaine was started at 3ml per hour. Three days later, when 1% mepivacaine 3ml was injected into the catheter, she complained of diplopia immediately and we recognized in her right eye other symptoms: disturbance of outside movement, weakness of light reflex and mydriasis. The catheter was positioned 4cm deeper than at the time of catheterization. Because we suspected catheter migrated into the subdural space, contrast medium was injected via the catheter. The catheter reached the C₂ vertebra, and the contrast medium reached the basilar region. Her symptoms faded within 2 hours. We suspected that neck movement caused catheter migration in the cranial direction and that the tip of the catheter broke through the dura mater. Subdural block by mepivacaine led to blockade of the oculomotor and abducent nerves, but the small dose of mepivacaine caused no other serious complications. After catheter removal, there were no sequelae. It is important to confirm the position of the catheter and neurological findings, even if there are no serious complications at the time of catheter insertion.

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A 40-year-old man developed urinary retention after herpes zoster involving the 3rd to 5th sacral dermatomes. He died 6 weeks after the onset of urinary retention until which time an indwelling urinary catheter was needed. The antibody titers against varicella-zoster virus in the cerebrospinal fluid and sera suggested intrathecal production of antibodies against varicella-zoster virus.

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Intractable hiccup is painful symptom obstructing ordinary ventilatory movement. We describe a 71-year-old patient, who had intractable hiccup associated with hepatoma, could not obtain sustained response to continuous cervical epidural blockade and was treated by baclofen. Although continuous cervical epidural blockade was effective, discontinuing epidural block therapy resulted in a recurrence of the symptom. Stellate ganglion block and phrenic nerve block were also ineffective and the patient complained of increasing dyspnea. 8 months later, the patient was given baclofen, a GABA-B receptor agonist, and the hiccuping completely resolved. Since then the patient has remained hiccup-free on baclofen for 23 months until his death due to massive hepatic hemorrhage from hepatoma. Our results suggest that baclofen may be indicated for patients with intractable hiccup resistant to several types of nerve block.

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Spinal anesthesia occasionally induces temporary but severe phantom limb pain in patients with a prior lower extremity amputation. Furthermore, there have been reports that spinal anesthesia induces severe lightning pain in the lower limb of patients with tabes dorsalis, diabetic neuropathy, subacute myelo-optico-neuropathy, and leprosy. We report a case in which midazolam completely prevented the generation of spinal anesthesia-induced phantom limb pain.
A 78-year-old man was scheduled for ureterocystoscopy. The patient had undergone right lower limb amputation 47 years previously, but had no history of phantom limb pain. Spinal anesthesia was uneventfully introduced using bupivacaine, which caused severe phantom limb pain occurred within five minutes. Intravenous administration of 2.0mg midazolam abolished the pain completely. The patient underwent ureterocystoscopy again 10 days later. After intravenous administration of 1.0mg midazolam, spinal anesthesia was uneventfully introduced. This time, no phantom limb pain developed throughout the examination.
Midazolam abolished phantom limb pain in the first intervention and might have prevented its appearance in the second. As possible mechanisms, midazolam may inhibit abnormal firings at the dorsal horn level, and/or rapid decrease in GABA levels in the sensorimotor cortex, both associated with deafferentation by spinal anesthesia.
This case suggests that preemptive administration of midazolam can prevent the development of spinal anesthesia-induced phantom limb pain.

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We report a case in which visual impairments due to optic neuritis, such as a dyschromatopsia and a metamorphopsia, were remarkably improved by stellate ganglion blocks (SGBs). A 60-year-old woman complained of bilateral visual disturbances after common cold-like symptoms. Her visual problem was diagnosed as optic neuritis on ophthalmologic examination and an aggressive steroid therapy was prescribed. However, visual impairments in her left eye persisted despite therapy. Sixteen months later, she received repeated left-sided SGB for treatment of Raynaud's phenomena of her hands. She noticed a gradual improvement of visual disturbances in her left eye after the 7th SGB. Her visual symptoms dramatically improved after the completion of 23 SGBs over more than 6 months. We, therefore, recommend SGB therapy in cases of old or fresh optic neuritis.

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A 30-year-old male presented with occasional occipital pain and paresthesia in half of his tongue on head turning. Several examination were performed, and his condition was diagnosed as neck tongue syndrome. After being intermittent for a few years, the symptoms gradually became incapacitating. Since NSAIDs and physical therapy didn't lead improvement in symptoms, treatment was initiated by stellate ganglion block (SGB) with 1% lidocaine 3 times a week. 10 SGB treatments resulted in decreased symptoms.

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We retrospectively examined the incidence of unilateral paresthesia of the lower extremities associated with postoperative epidural analgesia in our hospital. In half a year, 896 patients received continuous epidural analgesia postoperatively. The number of patients who complained of unilateral paraesthesia in the morning after operation was 37 (4.1%), and in 4 out of these 37 patients paresthesia was accompanied by apparent muscle weakness in the lower extremities. In 36 patients, the symptoms disappeared within 3 hours after the removal of the catheter. It should be noted that 19% of these patients requested the removal of the catheter even after we explained the reversibility of these symptoms and the effective analgesia attained by the catheter. Although these complications were reversible in this investigation, it is important to differentiate them from irreversible nerve injury and to make the epidural analgesia more acceptable to patients.

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The patient consulted another institution with a two-year history of pain radiating from the precordial and scapular regions to the axilla. However, despite thorough investigations, the cause of the pain could not be identified. The patient was subsequently referred to our department for the management of intractable pain, and was undergoing nerve block and drug therapy. While on these treatments, the patient began to complain of unilaterally reduced facial and palmar sweating associated with a warm sensation, and diagnostic imaging (CT and MRI) performed at this time detected apical lung cancer. In this patient, clear signs of sympathetic blockade including reduced sweating and increased skin temperature were seen, although Horner syndrome was not observed. When treating cryptogenic radiating pain in the shoulder and the upper arm, therapy such as stellate ganglion block is often performed, but medical inquiry and diagnostic imaging are important when considering the treatment of patients with this type of intractable pain. Since it is particularly difficult to detect subjective and objective symptoms associated with autonomic nerve abnormalities, autonomic activity must be assessed.

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