Pain
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Randomized Controlled Trial Comparative Study Clinical Trial
Rofecoxib attenuates both primary and secondary inflammatory hyperalgesia: a randomized, double blinded, placebo controlled crossover trial in the UV-B pain model.
The analysis of drug's influence on peripheral and central sensitisation can give useful information about its mode of action and can lead to more efficacy in the treatment of pain. Peripheral inflammation is associated with peripheral expression and up-regulation of cyclooxygenase 2 (COX-2) in the CNS. The relative contribution of COX-2 mediated central sensitisation may be prominent under inflammatory conditions. ⋯ No significant difference between the three dosage groups was observed. These data confirm peripheral effects of rofecoxib in a human inflammatory UV-B pain model and provide circumstantial evidence that even a standard clinical dose of rofecoxib reduces central hyperalgesia in inflammatory pain. We confirm that the effect of single oral dose of rofecoxib plateaus at 50 mg.
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Randomized Controlled Trial Comparative Study Clinical Trial
The effects of racemic ketamine on painful stimulation of skin and viscera in human subjects.
Evidence suggests that NMDA receptors may have a differential role in the modulation of visceral and somatic pain. Specifically, animal data indicate an analgesic role of NMDA-R antagonists in acute visceral but not acute somatic pain. In humans analgesic effects are documented in acute somatic pain, while the role of NMDA-R antagonists in acute visceral pain is still questionable. ⋯ In addition, ketamine did not alter the perception of innocuous stimuli in either modality. Our results confirm the analgesic effects of low-dose ketamine, with minimal side effects, on acute visceral pain and indicate a similar but smaller effect on acute cutaneous pain. A decrease in the unpleasantness but not in the intensity of cutaneous pain may reflect the differential effect of NMDA-R antagonists for the two pain states observed in animal models.
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Comparative Study Clinical Trial
Significantly higher methadone dose for methadone maintenance treatment (MMT) patients with chronic pain.
The aim of this study is to characterize patients with chronic pain in methadone maintenance treatment (MMT). Between September and December, 2003, 170 consecutive patients from an MMT clinic participated in a questionnaire survey on pain (duration and severity). Chronic pain was defined as current pain lasting for >or=6 months. ⋯ Patients in the non-pain group (n=76) were receiving 147.1+/-52.8 mg/day of methadone (ANOVA, F=3.1, P=0.03). We conclude that pain duration and severity significantly correlated. Although methadone was not prescribed for the treatment of pain but rather for opiate addiction, the patients in the MMT clinic with prolonged pain were prescribed a significantly higher methadone dosage compared to patients with short pain duration, and non-pain patients.
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Comparative Study
Pronociceptive role of dynorphins in uninjured animals: N-ethylmaleimide-induced nociceptive behavior mediated through inhibition of dynorphin degradation.
Intrathecal (i.t.) administration into mice of N-ethylmaleimide (NEM), a cysteine protease inhibitor, produced a characteristic behavioral response, the biting and/or licking of the hindpaw and the tail along with slight hindlimb scratching directed toward the flank. The behavior induced by NEM was inhibited by the intraperitoneal injection of morphine. We have recently reported that dynorphin A and, more potently big dynorphin, consisting of dynorphins A and B, produce the same type of nociceptive response whereas dynorphin B does not [Tan-No K, Esashi A, Nakagawasai O, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. ⋯ NEM completely inhibited degradation of dynorphin A by soluble and particulate fractions of mouse spinal cord. Collectively, the results demonstrate that endogenous prodynorphin-derived peptides are pronociceptive in uninjured animals, and required for the NEM-induced behavior. The NEM effects may be mediated through inhibition of the degradation of endogenous dynorphins, presumably big dynorphin that in turn activates the NMDA receptor ion-channel complex by acting on the polyamine recognition site.
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Comparative Study
Spinal noradrenaline transporter inhibition by reboxetine and Xen2174 reduces tactile hypersensitivity after surgery in rats.
Spinal noradrenaline (NA) released in response to noxious stimuli may play an important role in suppression of nociceptive transmission. Here, we investigated the efficacy of a competitive NA transporter inhibitor (reboxetine) and a noncompetitive NA transporter inhibitor peptide, Xen2174, isolated from the Pacific cone snail, to treat tactile hypersensitivity following paw incisional surgery. Male Sprague-Dawley rats were anesthetized, an incision of the plantar aspect of the hind paw was performed, and withdrawal threshold to von Frey filaments near the surgical site determined. ⋯ The anti-hypersensitivity effect of 10 microg of Xen2174 was totally blocked by the alpha2-adrenoceptor antagonist, idazoxan, and partially blocked by the muscarinic antagonist, atropine. These data suggest that selective NA transporter inhibition suppresses post-incisional hypersensitivity through a different mechanism from that of neuropathic pain, since we previously reported that reversal of hypersensitivity by intrathecal clonidine, an alpha2-adrenoceptor agonist, following spinal nerve ligation is completely blocked by intrathecal atropine. Finally, these data suggest that intrathecal administration of Xen2174 at the time of spinal anesthesia might produce postoperative analgesia in humans.