Articles: hyperalgesia.
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J. Pharmacol. Exp. Ther. · Oct 2003
Capsaicin-induced hyperalgesia and mu-opioid-induced antihyperalgesia in male and female Fischer 344 rats.
The influence of sex in determining responses to opioid analgesics has been well established in rodents and monkeys in assays of short-lasting, phasic pain. The purpose of this investigation was to use a capsaicin model of tonic pain to evaluate sex differences in hyperalgesia and mu-opioid-induced antihyperalgesia in Fischer 344 (F344) rats. Capsaicin injected into the tail produced a dose-dependent thermal hyperalgesia in males and females, with the dose required to produce a comparable level of hyperalgesia being 3.0-fold higher in males than in females. ⋯ When administered locally, the antihyperalgesic effects of morphine were mediated by peripheral opioid receptors in both males and females, since this effect was not reversed by i.c.v. naloxone methiodide. These data contrast with the finding that mu-opioids are more potent in male rodents in assays of phasic pain, thus suggesting that distinct mechanisms underlie male and female sensitivity to opioid antinociception in phasic and tonic pain models. These findings emphasize the need to test male and female rodents in tonic pain assays that may have greater relevance for human pain conditions.
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In male rats, carrageenan (CAR)-induced inflammation or exposure to a selective protein kinase C epsilon (PKC epsilon ) agonist (psi epsilon RACK) produces prolongation of the hyperalgesia induced by a subsequent exposure to an inflammatory mediator, a phenomenon referred to as hyperalgesic priming. Since many chronic inflammatory conditions are sexually dimorphic, we tested the hypothesis that hyperalgesic priming is sexually dimorphic. Prior injection of CAR or psi epsilon RACK produced a prolongation of the hyperalgesia induced by a subsequent injection of prostaglandin E(2), from less than 3 h to greater than 24 h, but only in male rats. ⋯ While gonadectomy in males had no effect on CAR and psi epsilon RACK induced hyperalgesic priming, female phenotype was observed following implantation of estrogen in males. Thus, mechanisms mediating the development of hyperalgesic priming produced by inflammation are suppressed by estrogen. This regulation of priming by estrogen appears to occur at or downstream of the activation of PKC epsilon.
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Irritable bowel syndrome (IBS) is one of the most common gastrointestinal illnesses and is characterized by altered visceral perception. The aim of the study was to determine if local anesthetic blockade of peripheral visceral nociceptive input reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. Ten women with IBS (mean age 30+/-10 years) and ten control subjects (all women) (mean age 29+/-7 years) rated pain intensity and unpleasantness to distension of the rectum (35 mmHg) and thermal stimulation (47 degrees C) of the foot before and after rectal administration of either lidocaine jelly or saline jelly in a double blind crossover design. ⋯ The results of this study support the hypothesis that local anesthetic blockade of peripheral impulse input from the rectum/colon reduces both visceral and cutaneous secondary hyperalgesia in IBS patients. The results provide further evidence that visceral hyperalgesia and secondary cutaneous hyperalgesia in IBS reflects central sensitization mechanisms that are dynamically maintained by tonic impulse input from the rectum/colon. Rectal administration of lidocaine jelly may also be a safe and effective means of reducing pain symptoms in IBS patients.
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Randomized Controlled Trial Comparative Study Clinical Trial
Intrathecal, but not intravenous adenosine reduces allodynia in patients with neuropathic pain.
Intrathecal adenosine reduces allodynia from intradermal capsaicin in human volunteers, and reduces hypersensitivity to mechanical stimuli in animals with nerve injury. Although both intrathecal and intravenous adenosine have been reported to relieve pain in patients with neuropathic pain, there are no controlled trials of this therapy. In order to determine the effect of adenosine, seven patients with chronic neuropathic pain and stable areas of mechanical hyperalgesia and allodynia were recruited. ⋯ Intrathecal, but not intravenous adenosine, caused backache in five of seven patients, lasting 6 h. These results indicate that intrathecal adenosine reduces allodynia and pain from stimulation in the area of allodynia, whereas the same dose of adenosine intravenously was ineffective. Given the modest effect and common side effects, the role for intrathecal adenosine as a sole agent for the treatment of neuropathic pain may be limited.