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It is not uncommon for patients with lung cancer to receive supportive care alone. However, the clinical characteristics of these patients have not been fully studied. We conducted a retrospective study to identify the clinical characteristics of definitive lung cancer patients treated with supportive care alone. We retrospectively analyzed the percentage of and reasons for definitive lung cancer patients treated with supportive care alone at a regional cancer center. We also investigated the histological diagnostic approaches, palliative therapy types, primary treatment locations after hospital consultation, and places of death. A total of 1,223 patients were histologically diagnosed as having lung cancer between 2011 and 2014. Of these, 160 (13%) patients were treated with supportive care alone. The primary reason for treatment with supportive care alone was a poor performance status (PS) in almost half of the patients. Overall, 40% of the patients received supportive care at home, and 17% were admitted to a palliative care unit (PCU). Death occurred at home for 17% of the patients and in the PCU for 42% of the patients. This study revealed that 13% of histologically proven lung cancer patients were treated with supportive care alone, mostly because of a poor PS. Only 40% of these patients received home care, suggesting the need for a more accessible home care system for patients and their families.

The authors investigated the role of endogenously released nociceptin (also known as orphanin FQ) in spinal and supraspinal nociceptive transmission during the rat formalin test by examining the effect of intrathecal and intracerebroventricular injection of J-113397, a non-peptidyl ORLI receptor selective antagonist. When J-113397 was injected intrathecally or intracerebroventricularly 10 min before the formalin injection, it enhanced the agitation behavior induced by paw formalin injection. This suggested that paw formalin injection induced nocicetpin release in the spinal cord and the supraspinal brain sites, that this endogenously released nociceptin produced an analgesic effect and that J-1 13397 antagonized this analgesic effect of nociceptin and produced an algesic effect in the rat formalin test.

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

Recently, opioid receptor like1 (ORL1) receptor was identified. The ORL1 receptor is a G protein coupled receptor and the sequence of the ORL1 receptor is closely related to that of the opioid receptors. Nociceptin/orphanin FQ has been identified as a potent endogenous agonist of the ORL1 receptor and the sequence of nociceptin/orphanin FQ is closely related to that of dynorphin A. Nociceptin/orphanin FQis not active at the classical opioid receptors, such as mu, kappa and delta receptors. The distribution of prepronociceptin mRNA is distinct from that of the opioid peptide precursor. Mice lacking the ORL1 receptor showed no significant differences in nociceptive threshold compared with wild mice. The role of nociceptin/orphanin FQ on nociceptive transmission is unclear. Intracerebroventricular (i.c.v.) injection of nociceptin/orphanin FQ produced hyperalgesia and allodynia and antagonized morphine analgesia. On the other hand, intrathecal injection of low dose nociceptin/orphanin FQ produces allodynia, but high dose of nociceptin/orphanin FQ produces an analgesic effect. Although we do not fully understand the mechanisms that produce the difference between the effect of i.c.v. injection of nociceptin/orphanin FQ and that of intrathecal injection of nociceptin/orphanin FQ, we believe that spinal ORL1 receptor may be the next receptor which should be targeted by drugs designed for the treatment of pain.

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.

N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) hydrolyzes N-acetyl-aspartyl-glutamate (NAAG) to liberate N-acetyl-aspartate and glutamate. NAAG is a putative neurotransmitter and acts as a mixed agonist/antagonist on N-methyl-D-aspartate (NMDA) receptors and acts as an agonist on the metabotropic glutamate receptor 3 (mGluR3). In the present study, we examined the role of spinal NAALADase in the maintenance of mechanical allodynia induced by carrageenan injection, skin incision and mild thermal injury using 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a specific NAALADase inhibitor, in rats. Mechanical allodynia was induced by injection of 2 mg carrageenan into the paw (carrageenan model), by creating a 1-cm longitudinal skin incision of the plantar aspect of the foot (post-operative model), or by application of thermal stimulation (52.5 degrees C) for 45 s to the hind paw (mild thermal injury model). 2-PMPA was administered intrathecally at the time when the maximum mechanical allodynia occurred. Mechanical allodynia was assessed by the measurement of mechanical threshold using von Frey filaments. The mechanical threshold was measured 5, 15, 30, 60 and 90 min after the drug administration. In the carrageenan model, 100 microg of 2-PMPA attenuated the level of mechanical allodynia. 2-PMPA had no effect on the level of mechanical allodynia in both the post-operative pain model and the mild thermal injury model. These data suggested that the inhibition of spinal NAALADase alleviated mechanical allodynia induced by paw carrageenan injection.

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.

Nocistatin is a 17 amino acid peptide and is processed from prepronociceptin. Nocistatin does not bind to the nociceptin receptor, but nocistatin blocks allodynia induced by nociceptin/orphanin FQ. In this study, we examined the effect of intrathecal nocistatin and its interaction with nociceptin/orphanin FQ in the rat formalin test and the hot plate test. Intrathecal nocistatin attenuated the formalin induced phase 1, but not phase 2, flinching behavior. Coadministration of nocistatin with nociceptin/orphanin FQ did not block the analgesic effect of nociceptin/orphanin FQ. Nocistatin had no effect on the hot plate test. These data suggest that nocistatin produces analgesic effect in the formalin test, but not in the hot plate test, and that the mechanisms underlying the analgesic effect of nocistatin is complex.

CYCLOOXYGENASE (COX)-2 is constitutively expressed in the superficial dorsal horn of the spinal cord, but its role in the spinal cord is still unclear. We examined the effect of intrathecally administered NS398, a selective COX-2 inhibitor and indomethacin, an non-selective COX-1 and COX-2 inhibitor, on the development of thermal hyperalgesia induced by the activation of NMDA or AMPA receptors. Intrathecal injection of either NS398 or indomethacin equally blocked the development of thermal hyperalgesia induced by intrathecal injection of either NMDA or AMPA in a dose-dependent manner. These data suggest that COX-2 plays an important role in spinal thermal nociceptive transmission when neurons in the spinal cord are facilitated by NMDA or AMPA.

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.

We investigated the effects of intrathecally administered N-type and P-type voltage-sensitive calcium channel (VSCC) blockers on the level of thermal hyperalgesia in two neuropathic pain models: the chronic constriction injury (CCI) model and the partial sciatic nerve injury (PSNI) model. N-type, but not P-type, VSCC blockers attenuated the level of thermal hyperalgesia induced by CCI in a dose-dependent manner. In the PSNI model, both N-type and P-type VSCC blockers had no effect on thermal hyperalgesia. This suggests that some types of neuropathic pain may be treatable with N-type VSCC blockers.

Progress in the development of O2-HIP equipment is described in this paper regarding safety and the achievement of a new high temperature O2-HIP apparatus.

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.