Pain
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Comparative Study
Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides.
In this study we investigated how the peptides derived from the glucocorticoid-inducible protein annexin 1 are able to alter the nociceptive threshold of mice. The effects of the annexin1 fragment 2-26 (Anxa1(2-26)) on nociceptive threshold were studied using both chemical (formalin test) and thermal (hot plate and tail flick test) nociceptive stimuli on mice. Subcutaneous administration of Anxa1(2-26) into the dorsal surface of the mouse's hind paw was able to selectively reduce formalin-induced nociceptive behavior in the last phase of the test. ⋯ We found that the formyl peptide receptor agonist formyl-MLF (fMLF) induced anti-nociceptive effects in the formalin test both after the peripheral and central administration. The formyl peptide receptor antagonist N-t-butoxycarbonyl-MLP did not alter the response to formalin, but it was able to block the anti-nociceptive effects of Anxa1(2-26,) Anxa1(2-12) and fMLF after peripheral or central administration. These results indicate that exogenously administered Anxa1 can peripherally and centrally inhibit the nociceptive transmission associated with inflammatory processes through a mechanism that involves formyl peptide receptors.
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Comparative Study
Evidence that CB-1 and CB-2 cannabinoid receptors mediate antinociception in neuropathic pain in the rat.
The roles of the two cannabinoid receptor subtypes, CB-1 and CB-2, have not been clarified in cannabinoid-mediated analgesia. We investigated the efficacy of the non-selective cannabinoid receptor agonist CP55,940 in the modulation of responses in the rat to both acute pain (tail flick) and neuropathic pain (tactile allodynia following chronic L5/6 spinal nerve ligation). Responses were also assessed in the presence of the CB-1 antagonist SR141716A (SR1) and the CB-2 antagonist SR144528 (SR2). ⋯ CP55,940 on both tail flick antinociception and tactile allodynia (P<0.005). The combination of SR1 and SR2 (i.p.) had an additive effect in decreasing the antinociception induced by CP55,940 on tail flick responses (P<0.005). These results suggest a role for CB-2 receptor-mediated antinociception in both acute and neuropathic pain in addition to centrally located CB-1 mechanisms.
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Comparative Study
Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model.
Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals, and activation of ERK in dorsal horn neurons by noxious stimulation is known to contribute to pain hypersensitivity. In order to elucidate the pathophysiological mechanisms of the cauda equina syndrome, secondary to spinal canal stenosis, we evaluated walking dysfunction triggered by forced exercise and activation of ERK in the dorsal horn using a rat model of neuropathic intermittent claudication. Rats in the lumbar canal stenosis (LCS) group showed a shorter running distance from 1 to 14 days after surgery. ⋯ In addition, a prostaglandin E1 analog, OP-1206 alpha-CD, administered orally, improved the walking dysfunction, and further, inhibited activation of ERK following running 7 days after surgery. These findings suggest that intermittent claudication triggered by forced walking might affect the phosphorylation of ERK in the superficial laminae, possibly via transient (partial) ischemia of the spinal cord. ERK activation in the dorsal horn neurons may be involved in the transient pain in the neuropathic intermittent claudication model.
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Comparative Study
Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy.
Paclitaxel (Taxol) is one of the most effective and frequently used chemotherapeutics for the treatment of solid tumours. However, paclitaxel produces peripheral neurotoxicity with patients reporting sensory abnormalities and neuropathic pain during and often persisting after paclitaxel therapy. The mechanisms underlying this dose-limiting side effect are currently unknown and there are no validated drugs for its prevention or control. ⋯ Repetitive dosing with ethosuximide (i.p. 100 or 300 mg/kg daily for 3 days) showed a dose-related consistent reversal of mechanical allodynia/hyperalgesia with no evidence of tolerance. Ethosuximide (i.p. 300 mg/kg) also reversed paclitaxel-induced cold allodynia and vincristine-induced mechanical allodynia/hyperalgesia. These data suggest that T-type calcium channels may play a role in chemotherapy-induced neuropathy and moreover identify ethosuximide as a new potential treatment for chemotherapy-induced pain.