Articles: hyperalgesia.
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It has been postulated that physical immobilization is an essential factor in developing chronic pain after trauma or surgery in an extremity. However, the mechanisms of sustained immobilization-induced chronic pain remain poorly understood. The present study, therefore, aimed to develop a rat model for chronic post-cast pain (CPCP) and to clarify the mechanism(s) underlying CPCP. ⋯ A sciatic nerve block with lidocaine 24 h after cast removal transitorily abolished bilateral mechanical hyperalgesia in CPCP rats, suggesting that sensory inputs originating in the immobilized hindlimb contribute to the mechanism of both ipsilateral and contralateral hyperalgesia. Intraperitoneal injection of the free radical scavengers 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxy1 or N-acetylcysteine 24 h after cast removal clearly inhibited mechanical hyperalgesia in bilateral calves and hindpaws in CPCP rats. These results suggest that cast immobilization induces ischaemia/reperfusion injury in the hindlimb and consequent production of oxygen free radicals, which may be involved in the mechanism of widespread hyperalgesia in CPCP rats.
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The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. ⋯ Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.
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Recent studies have suggested that activated glia in the spinal cord may play a vital role at different times during spinal nerve ligation (SNL)-induced neuropathic pain; therefore, glial activation inhibitors have been used as effective painkillers. Brain-derived neurotrophic factor (BDNF) is also known to be a powerful pain modulator, but it remains unclear how it contributes to the glial activation inhibitor-based treatment. This study revealed the following results: (1) intrathecal administration of minocycline (a microglial activation inhibitor) could prevent mechanical allodynia during the initiation of SNL-induced neuropathic pain, and its action was associated with the elimination of BDNF overexpression in the dorsal horn; (2) the spinal injection of fluorocitrate (an astrocytic activation inhibitor) but not minocycline could reverse mechanical allodynia during the maintenance phase of SNL-induced pain, and its action was also related to a decrease in BDNF overexpression in the dorsal horn; and (3) treatment with TrkB/Fc (a BDNF-sequestering protein) had a similar effect during both the early development and maintenance periods. These results led to the following conclusions: (1) elevated BDNF expression in the dorsal horn was required to develop and maintain neuropathic pain; (2) minocycline could only prevent mechanical allodynia in the early stages, possibly by inhibiting BDNF release from microglia; and (3) fluorocitrate could reverse existing mechanical allodynia, and its action was associated with the inhibition of BDNF upregulation induced by astrocytic activation.
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Although some studies have shown the essential role of descending serotonergic pathways and spinal 5-HT(1A), 5-HT(2A), or 5-HT(3) receptors in the antinociceptive effects of paracetamol, other studies have presented conflicting results, and the particular subtype of spinal 5-HT receptors involved in paracetamol-induced analgesia remains to be clarified. Recent studies have demonstrated the importance of spinal 5-HT(7) receptors in descending serotonergic pain inhibitory pathways. In this study, we investigated the role of descending serotonergic pathways and spinal 5-HT(7) receptors compared with 5-HT(3) and 5-HT(2A) receptors in the antinociceptive and antihyperalgesic effects of paracetamol. ⋯ Depletion of spinal 5-HT totally abolished the antinociceptive and antihyperalgesic effects of paracetamol. I.th. injection of SB 2669970 (10 μg) blocked the antinociceptive and antihyperalgesic effects of paracetamol, but ondansetron and ketanserin (10 μg) did not. Our findings suggest that systemic administration of paracetamol may activate descending serotonergic pathways and spinal 5-HT(7) receptors to produce a central antinociceptive and antihyperalgesic effects.
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Neuroscience letters · Feb 2012
Role of neuronal nitric oxide synthase in the antiallodynic effects of intrathecal EGCG in a neuropathic pain rat model.
Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, is known to have antioxidant activity against nitric oxide (NO) by scavenging free radicals, chelating metal ions, and inducing endogenous antioxidant enzymes. NO and NO synthase (NOS) play an important role in nociceptive processing. In this study, we examined the effects of intrathecal EGCG in neuropathic pain induced by spinal nerve ligation and the possible involvement of NO. ⋯ This antinociceptive effect was reversed by intrathecal pretreatment with l-arginine, a precursor of NO. Intrathecal EGCG also blocked the increase in nNOS expression in the spinal cord of spinal nerve-ligated rats, but iNOS expression was not significantly suppressed. These findings suggest that intrathecal EGCG could produce an antiallodynic effect against spinal nerve ligation-induced neuropathic pain, mediated by blockade of nNOS protein expression and inhibition of the pronociceptive effects of NO.