Intradermal injection of melittin, the main toxin of honeybee venom, into the forearm in humans produced an axon reflex-mediated temperature increase in the local skin. In addition, melittin produced a temporary skin temperature decrease due to the sympathetic vasoconstrictor reflex and a subsequent increase due to the release of sympathetic vasomotor tone in both hands. In order to further investigate effects of melittin, skin temperature changes of anesthetized rats following a plantar injection of melittin were analyzed by thermography. An injection of either melittin or bee venom into the hindpaw produced a skin temperature increase, but apamine did not. There was a considerable individual variation in the axon reflex-mediated temperature increase in the hindpaw on the injection side. The hindpaw skin temperature on the non-injection side also slightly increased with a longer latency. The increase was more marked in rats with lower preinjection temperature. If melittin releases the sympathetic tone, skin temperature changes induced by the second injection may be different from those induced by the first injection. One hour later, the second melittin was injected into the hindpaw on the other side. The second injection similarly increased the hindpaw skin temperature on the second injection side in all rats, but did not affect the temperature of the contralateral hindpaw subjected to the first injection. These data suggest that subcutaneous melittin produced axon reflex and the decrease of the sympathetic activities in rats.

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   We studied the effect and the indication of various kinds of surgical treatment for central (thalamic) pain in 10 cases. In 3 cases with localized pain, epidural spinal cord stimulation was effective. In 7 cases with diffuse pain (hemibody), stereotactic Vim-Vcpc thalamotomy was performed with the aid of depth microrecording. In 4 of these cases in which pain relief was obtained, we could find responses to peripheral natural stimulation on the sensory thalamus during the operation. Preoperative PET study also revealed an increase of rCBF on the sensory cortex ipsilateral to the thalamic CVD lesion during contralateral thumb brushing. On the other hand, in the 3 cases in which we failed to obtain pain relief, we frequently encountered irregular burst discharges on the thalamus. Gamma thalamotomy was added after the conventional thalamotomy in these 3 cases. Though transient pain relief was obtained, pain recurred thereafter. Precentral electrical cortical stimulation was also carried out in 3 recurrent cases, resulting in the failure of pain relief. In one of these cases, internal capsular (posterior limb) stimulation was performed, obtaining encouraging result. In cases of localized thalamic pain, epidural spinal cord stimulation proved to be an effective treatment. Thalamic surgery achieved pain relief in those cases with diffuse type pain, limited to preserving sensory function on the sensory thalamocortical system. Precentral electrical cortical stimulation, internal capsular (posterior limb) stimulation or Gamma thalamotomy may be an alternative treatment for central (thalamic) pain.

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   Despite receiving postoperative thoracic epidural analgesia, severe shoulder pain on the ipsilateral side is common in patients after thoracotomy. The pain is relatively resistant to IV opioids or moderate doses of non steroidal antiinflammatory drugs, and increasing doses of the epidural analgesic to achieve adequate analgesia may result in unacceptable levels of sedation and hypotension. Effective analgesia for postthoracotomy shoulder pain has been achieved by infiltrating local anesthetics around the phrenic nerve, however, there is a potential problem of diaphragmatic dysfunction and the associated risk of respiratory depression. We investigated whether trigger-point injection with lidocaine would treat postthoracotomy shoulder pain effectively.
   Methods: Trigger-point injection with lidocaine was performed in 11 patients who complained shoulder pain after the thoracotomy surgery. All patients received general anesthesia combined with a midthoracic epidural anesthesia. Eleven patients complained shoulder pain after thoracotomy surgery, and all of them had trigger-points in the ipsilateral suprascapular regions with severe pain. After disinfecting the skin at the two or three most painful trigger-points, 1% lidocaine were injected IM into one side of the trapezius muscle by using a 25-gauge needle. Shoulder pain was assessed before and immediately after the injection, using a 10-point verbal ranking score (VRS), and VRS before the injection point were considered as 10. Data were expressed as mean ± SD.
   Results: There were significant (p<0.05) decreases in VRS after the injection. VRS score were 4.6 ± 3.1 immediately after the injection, showing significantly less (p<0.05) pain after the injection.
   Conclusions: This result suggests that this pain observed is likely a sort of myofascial pain syndrome due to possible intraoperative positioning. Trigger-point injection is an effective and safe alternative to relief of ipsilateral shoulder pain after thoracotomy.

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   Background: Poststroke central pain is often refractory to conventional treatment such medication or neurosurgical interventions, and development of new treatment modality is mandatory. Despite of general belief, chemical hypophysectomy is reported to alleviate thalamic pain with long-lasting effect. Based on our experience of gamma-kinfe hypophysectomy for cancer pain, we evaluated the effect of gamma-knife irradiation to the pituitary stalk on intractable poststroke central pain.
   Subjects and Methods: Eight patients with intractable thalamic pain were enrolled in this study. Three of them had undergone surgical procedures for the pain without benefit. Other patients were considered not suitable for surgical interventions because of the general condition such as chronic renal failure and a history of cardiac problems. Gamma-knife was targeted to the border between the pituitary stalk and the gland, and maximum dose of 140 Gy was delivered. The irradiation dose to the optic pathway was controlled to less than 8 Gy.
   Results: All patients except one reported marked pain relief (70–100%, mean 75%) within 1–7 days (mean 2.7 days) after the gamma-knife treatment. One patient experienced recurrence of pain after one month to the pre-treatment level, while other six patients reported lasting effect of pain relief during the follow-up period (8–11 months). One patient showed transient diabetes insipidus. No other complications were noted. There were no changes of pituitary hormone tests and visual fields.
   Conclusion: Although longer follow-up is indispensable, the initial preliminary results indicate that gamma-knife irradiation to the pituitary stalk may become a useful treatment for otherwise intractable poststroke central pain.

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   Marijuana (Cannabis sativa) has a large variety of therapeutic effects including analgesia, all of which are thought to be due to an action of its primary active constituent, ∆⁹-tetrahydrocannabinol, acting on cannabinoid receptors. Endocannabinoids such as N-arachidonoylethanolamide (anandamide) are also known to exert antinociceptive activity in various animal models of acute pain. A subtype of cannabinoid receptors, CB1, is predominantly expressed in the CNS including the spinal superficial dorsal horn. Although a number of studies have examined an action of cannabinoids on synaptic transmission in the CNS, this is not understood fully in the spinal dorsal horn. In order to know a role of cannabinoids in regulating pain transmission, we studied the effects of anandamide and a synthetic cannabinoid-receptor agonist, WIN-55212-2, on excitatory and inhibitory transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the blind whole-cell patch-clamp technique. In many of the cells examined, anandamide (10 µM) attenuated the amplitude of either monosynaptic glutamatergic EPSCs through Aδ and C primary-afferent fibers, γ-aminobutyric acid (GABA) or glycine-mediated focally-evoked IPSCs. Spontaneous GABAergic and glycinergic IPSCs were inhibited in frequency but not amplitude by anandamide, while spontaneous EPSCs were unaffected in amplitude and frequency. These actions were mimicked by WIN-55212-2 (5 µM). It is concluded in SG neurons that can nabinoids inhibit the release of L-glutamate from primary-afferent central terminals and also the release of GABA and glycine from interneuron terminals, all of which are possibly due to the activation of the CB1 receptor; these actions would contribute to a modulation of nociceptive transmission to the spinal dorsal horn from the periphery.

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   We reported four patients who received the treatment for severe pain with normal saline and/or distilled water injections. They suffered from various kinds of severe pain. The diagnoses were, a chest pain from bone metastases of terminal liver cancer (Case 1), a low back and leg pain from lumbar spinal canal stenosis (Case 2), a scar pain after thoracic drainage (Case 3) and a postherpetic pain in cervical region (Case 4). All patients received the treatment consisted of nonsteroidal anti-inflammatory drugs (NSAIDs) and pentazocine and/or continuous epidural block, but pain relief was a little and incomplete. While they requested more potent pain relieving measures, but received injections of normal saline and/or distilled water. They recognized that “analgesic” injections had either some effect or no effect, but their physicians thought of the complaints as “psychogenic”one. After consulting to our clinic, we informed them in detail about the treatments with morphine and/or codeine. All 4 patients received our proposal, oral codeine (Case 2, 3) or continuous intravenous/oral morphine (Case 1, 4) started. Pain effectively relieved in all cases with satisfaction. In the treatment of pain, the word, “believe the patient's report of pain”, is the most fundamental principle. When patients complain of pain, they really suffer from pain and want more potent or much doses of analgesic,not normal saline or distilled water ! At that time, physician should “believe the patient's report of pain” and provide reliable pain-relieving therapies.

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   A multicenter study was conducted to evaluate the efficacy and safety of AN-982, a unit-dose oral solution of morphine hydrochloride with a less bitter taste and improved stability at room temperature.
   Methods: AN-982 was administered to the following three types of patients:
1) Patients who were strong opioid naive and whose pain control was insufficient with non-opioid analgesics or weak opioids were started on an initial dose of 5 – 10 mg of AN-982 every 4 hours and the dose was titrated to achieve adequate analgesia (new subjects).
2) Patients being treated with other immediate-release oral morphine formulations were switched to AN-982 using the same dose and dosing interval as those of the other immediate-release oral morphine (switched subjects).
3) Patients being treated with Controlled Release Morphine Sulfate tablets who had “breakthrough” pain were administered AN-982 as the rescue medication (rescued subjects).
   Results:
1) The efficacy rate in new subjects, switched subjects, and rescued subjects was 97.0% (32/33), 100% (9/9), and 77.5% (31/40), respectively.
2) Adequate pain relief was achieved on the first day of administration in 55.6% (15/27) of the new subjects, and the average time required to achieve adequate pain relief was 2.1 days.
3) In the switched subjects, adequate pain relief was achieved by administration of AN-982 at the same dose and dosing interval as those of the previous immediate-release oral morphine formulations.
4) In the rescued subjects, significant improvement of the pain and VAS scores were observed from 15 minutes after the administration of AN-982 and continued for 2 hours.
5) The overall incidence of adverse reactions was 74.1% (63/85) after AN-982 administration, and the incidence was similar to that observed with controlled-release morphine tablets during development. The most frequent adverse reactions were constipation, nausea, vomiting, and drowsiness, which are all well-known side effects of morphine.
   Conclusion: AN-982, a rapidly-acting oral solution of morphine hydrochloride, is not only effective and useful for pain management in cancer patients (as a regular analgesic and as rescue medication), but also assists medical personnel in preparing morphine formulations.

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