Articles: hyperalgesia.
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This article reports the development of a new hind limb pain model in which an incisional stab wound is placed on the front and back of the calf, causing both superficial and deep tissue injury. The injury causes primary mechanical hyperalgesia on the calf and secondary hind paw hyperalgesia, which served as the focus of the present study. Animals with unilateral stab wounds showed a significant increase in percent paw withdrawal (secondary mechanical hyperalgesia, reversed by morphine administration) from 2 to 48 hours after surgery, but no evidence of thermal hyperalgesia. In contrast, animals with bilateral leg injuries showed bilateral secondary mechanical and thermal hyperalgesia. Rats with unilateral leg incisional stab wounds showed a significant decrease in cage activity in both the horizontal and vertical directions, monitored by using a novel activity box approach, as compared to their 24-hour baseline levels or to the activity of naïve animals. Analysis of spinal cord Fos labeling demonstrated that calf injury significantly increased Fos expression in laminae I to VI of the L3-L5 cord segments. The data indicate that this model might be useful for evaluation of the mechanisms underlying penetrating injury-induced primary and secondary hyperalgesia or for testing the effect of analgesics on hyperalgesia induced by such injury. ⋯ Stab wounds and other types of penetrating wounds routinely encountered in emergency rooms and clinics are accompanied by pain associated with superficial and deep tissue injury. Here we present a rodent stab wound model that affords an opportunity to study the mechanisms of pain associated with traumatic injury.
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Arthritis and rheumatism · Feb 2004
Evidence of augmented central pain processing in idiopathic chronic low back pain.
For many individuals with chronic low back pain (CLBP), there is no identifiable cause. In other idiopathic chronic pain conditions, sensory testing and functional magnetic resonance imaging (fMRI) have identified the occurrence of generalized increased pain sensitivity, hyperalgesia, and altered brain processing, suggesting central augmentation of pain processing in such conditions. We compared the results of both of these methods as applied to patients with idiopathic CLBP (n = 11), patients with widespread pain (fibromyalgia; n = 16), and healthy control subjects (n = 11). ⋯ At equal levels of pressure, patients with CLBP or fibromyalgia experienced significantly more pain and showed more extensive, common patterns of neuronal activation in pain-related cortical areas. When stimuli that elicited equally painful responses were applied (requiring significantly lower pressure in both patient groups as compared with the control group), neuronal activations were similar among the 3 groups. These findings are consistent with the occurrence of augmented central pain processing in patients with idiopathic CLBP.
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J. Pharmacol. Exp. Ther. · Feb 2004
Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin.
The present studies were conducted to test the hypothesis that activation of peripheral cannabinoid CB(2) receptors would suppress hyperalgesia evoked by intradermal administration of capsaicin, the pungent ingredient in hot chili peppers. The CB(2)-selective cannabinoid agonist (2-iodo-5-nitro-phenyl)-[1-(1-methyl-piperidin-2-ylmethyl)-1H-indol-3-yl]-methanone (AM1241) (33, 330 microg/kg i.p.) suppressed the development of capsaicin-evoked thermal and mechanical hyperalgesia and allodynia. AM1241 also produced a dose-dependent suppression of capsaicin-evoked nocifensive behavior. ⋯ AM1241 (33 microg/kg i.pl.) suppressed capsaicin-evoked thermal and mechanical hyperalgesia and allodynia after local administration to the capsaicin-treated (ipsilateral) paw but was inactive after administration to the capsaicin-untreated (contralateral) paw. Our data indicate that AM1241 suppresses capsaicin-evoked hyperalgesia and allodynia through a local site of action. These data provide evidence that actions at cannabinoid CB(2) receptors are sufficient to normalize nociceptive thresholds and produce antinociception in persistent pain states.
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Neuroscience letters · Jan 2004
Differential expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 in normal and inflamed rats.
In an attempt to understand mechanisms underlying peripheral sensitization of primary afferent fibers, we investigated the presence of the tetrodotoxin-resistant Na+ channel subunits Nav1.8 (SNS) and Nav1.9 (SNS2) on axons in digital nerves of normal and inflamed rat hindpaws. In normal animals, 14.3% of the unmyelinated and 10.7% of the myelinated axons labeled for the Nav1.8 subunit. ⋯ These data indicate that Nav1.8 and Nav1.9 subunits are transported to the periphery in normal animals and are differentially regulated during inflammation. The massive increase in Nav1.8 expression in myelinated axons suggests that these may contribute to peripheral sensitization and inflammatory hyperalgesia.
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Arzneimittel Forsch · Jan 2004
Randomized Controlled Trial Clinical TrialEffect of the new H1-antagonist ReN1869 on capsaicin-induced hyperalgesia in human skin/Human phase-I trial using somatosensory evoked potentials induced by a CO2 laser.
Extensive pre-clinical investigations have shown that the tricyclic compound ReN1869 ((R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-propyl)-3-piperidine carboxylic acid, CAS 170149-99-2) is a potent H1-antagonist with pronounced antinociceptive properties. In this human phase-I trial the effect of different acute and multiple doses of ReN1869 on capsaicin induced neurogenic inflammation and hyperalgesia was investigated. Twenty-one healthy male subjects were enrolled in this randomised, double-blind, three-period, crossover trial design--consisting of acute and one week b.i.d. oral administration of 25 and 50 mg doses of ReN1869 and matching placebo--separated by 3 week washout periods. ⋯ This suppression was dose-dependent and was more pronounced after a one week treatment (subchronic mode) with ReN1869 than after the first dose (acute mode). In contrast to the (central) P2-component there was no significant effect on the (peripheral) N1-component of the LSEPs taken from capsaicin-treated skin. As ReN1869 had no significant effect when the laser pulses were applied to normal skin, and the compound's effect was mainly restricted to the (central) P2-component, when LSEPs were taken from capsaicin treated skin, it can be concluded that ReN1869 exerts its positive effect to reduce capsaicin-induced hyperalgesia by a primarily central mechanism.