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The role of PACAP receptor in nociceptive transmission was investigated in vitro using maxadilan, a PACAP receptor selective agonist and max.d.4, a PACAP receptor selective antagonist. Potentials, from a ventral root (L3 – L5) of an isolated spinal cord preparation or a spinal cord – saphenous nerve – skin preparation from 0 – 3-day-old rats, were recorded extracellularly. In the isolated spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of max.d.4 (0.01 – 3 μM) inhibited the slow VRP in a concentration-dependent manner. In the spinal cord – saphenous nerve – skin preparation, application of capsaicin (0.1 μM) to the skin evoked a depolarization of the ventral root. This response was also depressed by max.d.4 (1 μM). Application of maxadilan evoked a long-lasting depolarization in a concentration-dependent manner in the spinal cord preparation. In the presence of max.d.4 (0.3 μM), the concentration response curve of maxadilan was shifted to the right. Reverse transcription-polymerase chain reaction (RT – PCR) experiments demonstrated the existence of PACAP receptor and VPAC2 receptor in the neonatal rat spinal cord and [125I]-PACAP27 binding was displaced almost completely by maxadilan and max.d.4, but not by vasoactive intestinal peptide (VIP). These data indicate that PACAP receptor is dominantly distributed in the neonatal rat spinal cord. The present study suggests that PACAP receptor may play an excitatory role in nociceptive transmission in the neonatal rat spinal cord. British Journal of Pharmacology (2001) 132, 1769–1776; doi:10.1038/sj.bjp.0703980

Purpose: To examine the effect of a cyclooxygenase (COX)-2 inhibitor on the maintenance of mechanical allodynia induced by skin incision (an animal model of postoperative incident pain) in the rat. Also, to compare the effect of a COX-2 inhibitor with that of a nonselective COX-1 and COX-2 inhibitor and B2 receptor antagonist. Methods: A 1 cm longitudinal skin incision was made in the plantar aspect of the foot. JTE522 (1 – 100 mg·kg−1), a COX-2 inhibitor, indomethacin (1 – 30 mg·kg−1), a nonselective COX-1 and COX-2 inhibitor, or FR173657 (10 and 100 mg·kg−1), a bradykinin B2 receptor antagonist, was administered orally five minutes after the end of the surgery. The level of mechanical allodynia was assessed by measuring the frequency of foot withdrawal in response to the application of a 12.5 g on Frey filament at 2, 4, 6, 8 and 24 hr after the drug administration. Results: Oral administration of JTE522 or indomethacin attenuated the maximum response frequency in a dose-dependent manner at a dose between 1 and 30 mg·kg−1 (P

純酸素吸入は,より低濃度の酸素吸入時に比べ吸収性無気肺を起こしやすいことが実験的に示されている.そこで,麻酔導入時と抜管時の純酸素吸入が,臨床的に問題となる術後の酸素化障害や,無気肺を引き起こしているか否か検討を行なった.幽門側胃切除を予定された呼吸器合併症のない21例を対象とし,麻酔導入時と抜管時の各10分間,純酸素吸入を行なう群と40%酸素吸入を行なう群に分けて,術中から術後24時間までの動脈血酸素分圧,術直後と術後第1日の胸部X線写真を比較した.その結果,両群間で有意な差を認めず,麻酔導入,抜管時の吸入酸素濃度の差は術後の酸素化障害および無気肺の発生に寄与していなかった.

Background Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury. Methods A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected. Results In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw. Conclusions The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.

The development of an optical temperature measurement system has made ultra-high-temperature HIP processing feasible. Previously, HIPing at temperatures in excess of 2200°C was difficult to operate stably with the conventional W/Re thermocouple. Using the system developed, glassy carbon, which is expected to be used as the substrate in magnetic heads and hard disks was HIPed at 2600°C and 200 MPa and confirmed to be fully densified.

Postoperative incident pain is not easily treated with opioids. Mechanical hyperalgesia induced by skin incision in rats is one of the animal models of postoperative incident pain. It is thought that mechanical hyperalgesia is maintained by the sensitization of spinal dorsal horn neurons. The NK-1 receptor, the opioid receptor like1 (ORL1) receptor, and cyclooxygenase (COX)-2 reportedly are involved in the development of spinal sensitization. In this study, we clarified the role of the NK-1 receptor, the ORL1 receptor, and COX-2 in the maintenance of mechanical hyperalgesia induced by skin incision. A 1-cm longitudinal incision was made through skin and fascia of the plantar aspect of the right foot in the rat. Four hours after the skin incision, significant mechanical hyperalgesia developed. An ORL1 receptor agonist (nociceptin), NK-1 receptor antagonists (CP-96,345 and FK888), and COX-2 inhibitors (NS398 and JTE522) were administered intrathecally 4 h after the skin incision. An ORL1 receptor agonist and NK-1 receptor antagonists, but not COX-2 inhibitors, significantly attenuated the level of mechanical hyperalgesia induced by the skin incision. These findings suggest that the spinal ORL1 receptor and the NK-1 receptor play an important role in maintaining the mechanical hyperalgesia induced by skin incision.Intrathecal injection of an NK-1 receptor antagonist and an ORL1 receptor agonist may be effective for the treatment of postoperative incident pain.