Neuropathic pain is associated with hyperalgesia to noxious stimuli and allodynia, pain induced by tactile stimuli. Elucidation of mechanism of induction of allodynia is an intriguing issue from viewpoints of both basic research and pain management. Although sciatic nerve injury models have been employed for studies on neuropathic pain, we found that intrathecal administration of prostaglandin E₂ induced allodynia as well as hyperalgesia. Here I report recent progress of molecular mechanism of neuropathic pain including studies with knockout mice.

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Pain is initiated when noxious thermal, mechanical, or chemical stimuli excite the peripheral terminals of specialized primary afferent neurons called nociceptors. Many different kinds of ionotropic and metabotropic receptors are known to be involved in this process. Capsaicin, the main ingredient in ‘hot’ chili peppers, elicits burning pain by activating specific (vanilloid) receptors on sensory nerve endings. The cloned capsaicin receptor (VR1) is a nonselective cation channel with six transmembrane domains. When expressed heterologously in HEK293 cells or Xenopus oocytes, VR1 is activated not only by capsaicin but also by heat in the noxious range (>43°C) or by protons. VR1 function as a detector of multiple pain-producing stimuli was verified by a behavioral study in mice lacking VR1. Thus, VR1 plays an important role in nociception.
It has been proposed that ATP, released from different cell types, initiates the sensation of pain by acting predominantly on nociceptive ionotropic purinoceptors located on sensory nerve terminals. We examined the effects of extracellular ATP on VR1 activity. In cells expressing VR1, ATP increased the currents evoked by capsaicin or protons through activation of metabotropic P2Y₁ receptors in a PKC-dependent pathway. The involvement of G_{q 11}-coupled metabotropic receptors in the potentiation of VR1 response was confirmed in cells expressing both VR1 and M1 muscarinic acetylcholine receptors. In the presence of ATP, the temperature threshold for VR1 ctivation was reduced from 42°C to 35°C, such that normally non-painful thermal stimuli (i.e. normal body temperature) were capable of activating VR1. This represents a novel mechanism through which the large amounts of ATP released from damaged cells in response to tissue trauma might trigger the sensation of pain.

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We evaluated percutaneous lumbar discectomy with nerve blocking therapy in a cohort of 455 patients with herniated lumbar intervertebral disc. They either had or did not have authorized indications, but all had recurrent pain or only transient relief after discography followed by steroid injection. Within 10 days after surgery, nerve blocking was conducted, if necessary.
Result: The overall effectiveness rate was 59.8% after 1 month and 68.6% after 6 months. The effectiveness rates in 216 patients with authorized indications were 69.9 and 79.6% after 1 and 6 months, respectively. For the other 239 patients associated with lipping and/or vertebral canal narrowing, the rates were 50.6 and 58.6%, respectively. Post operative nerve blocking was particularly effective for zygapophyseal joints and lumbar sympathetic ganglions.
Conclusion: Additive and synergic effects of percutaneous lumbar discectomy with nerve blocking yielded adequate improvement in almost half of the patients without authorized indications.

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Analgesic efficacy and analgesic duration of radiofrequency lesion treament of the facet rhyzotomy were investigated in 61 patients in a randomized prospective study. Before treatment, the putative pain-provoking vertebral facet was identified by diagnostic blocks with a local anesthetic agent, and 124 cases were divided into 2 groups randomly. The low temperature group (n=62, group 1) was treated with a radiofrequency lesion of 45-50°C and in the high temperature group (n=62, group 2) a temperature of 60-65°C was applied. We assessed monthly the analgesic efficacy of the facet rhyzotomy for 12 months. The analgesic effect of the treatment in both groups was identical. The mean analgesic duration±SD was 6.7±4.0 months in group 1 and 7.1±3.6 months in group 2, respectively. There was no significant difference between the 2 groups. In 17 cases (27%) in group 1 and 12 cases (19%) in group 2, the analgesic effect of the treatment was continued more than 12 months. This study suggests that treatment with 45-50°C radiofrequency application of the facet thyzotomy is equally as effective as the treatment at 60-65°C.

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A 41-year-old woman underwent appendectomy under spinal anesthesia. A 22 G spinal needle was inserted into the sub-arachnoid space through the L₃₄ interspace, followed by the injection of 3.0ml 0.5% hyperbaric bupivacaine. The analgetic level was obtained adequately below T₈ bilaterally. During spinal anesthesia, her operative course was uneventful for 2.5 hours, and then anesthesia was maintained with nitrous oxide and sevoflurane in oxygen because of prolongation of the surgical procedure. On the first postoperative day, the patient complained of dysesthesia of the anterior aspects of the right thigh and leg, and walking disturbance. Magnetic resonance imaging (MRI) findings were normal. Neurological examination and electromyogram (EMG) revealed right femoral neuropathy, and the complication was determined to be due to the retractor compression during surgery. The administration of vitamin B₁₂, steroid, prostaglandin E₁ and epidural blockage improved dysesthesia, sensory loss and motor weakness. After 1.5 months, the patient completely recovered from the neurological symptoms. This case emphasizes the importance of excluding neurological complications encountered with spinal anesthesia.

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Objective: We produced a special needle for stellate ganglion block (SGB needle) to lessen tissue damage caused by puncture. The tip of the SGB needle is in the shape of a pyramid with sharp edges, and there is a hole for injection 1.5mm from the tip. The aim of this study was to investigate the special properties and clinical usefulness of the SGB needle. Methods: We experimentally compared damage at the puncture site and pressure needed for puncture of the SGB needle to those of a standard disposable needle. In addition, we examined the effect of SGB, complications, impressions of surgeons and complaints of patients, using this needle for 89 blocks in 19 patients. Results: The tissue damage caused by the SGB needle was smaller than, and the pressure needed for puncture was equivalent to that of a standard disposable needle. Clinical use of the SGB needle caused no problems with puncture or injection, and the nerve block was completely effective. There were neither major complications nor any subcutaneous bleeding or induration. Patients had no complaints about the SGB needle. Conclusion: This study indicates that the SGB needle is useful in clinical work.

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It has been reported that pain management by the PCA pump is useful. But many problems related with the use of computer-controlled mechanical PCA pump have been pointed out. Psychological stress both of patients and nurses were the main problems. From the analysis of these problems, explanation booklet of “before use” was introduced. How to handle the PCA pump itself, how to cope with alarm events, how to replace battery, and so on, were explained simply in this booklet. Explanation picture sheet was also introduced. Another unexpected problem was the obstruction of the line. We examined this obstruction phenomenon very carefully and concluded that the cause of obstruction was the air trap in the micro bacterial filter. After changing it to a filter with an air vent system, this obstruction alarm event disappeared. After the introduction of these easy-to-understand booklet, sheet, and micro bacterial filter with air vent system, dramatically big improvement was achieved.

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