Articles: hyperalgesia.
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Neuroscience letters · Jan 2012
Comparative StudyA direct comparison of affective pain processing underlying two traditional pain modalities in rodents.
In the preclinical study of pain, two commonly used pain models are the L5 spinal nerve ligation (SNL) and the injection of carrageenan. Using a modified place escape/avoidance paradigm (mPEAP), a novel behavioral test that quantifies aversive behavior evoked by painful stimuli, we directly compared the affective component of the SNL and inflammation models. Fifty three Sprague-Dawley rats underwent baseline mechanical paw withdrawal threshold (MPWT) and mPEAP testing followed by an L5 SNL or sham surgery for the left paw and then a carrageenan or saline injection for the right paw. ⋯ Animals with the bilateral pain condition did not show a preference for stimulation of one paw versus the other paw, and the avoidance behavior was not significantly different from the sham/saline control. The results indicate that the pain models are associated with significant avoidance behavior and that they produce comparable degrees of pain affect. These findings advance the preclinical study of pain by validating the simultaneous utilization of the SNL and inflammation models and will allow future studies that combine pain conditions to more closely resemble clinical conditions.
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Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system and treatment of neuropathic pain remains a challenge. The purpose of the present study was to examine the effect of ethosuximide, an anti-epileptic and relatively selective T-type calcium blocker and morphine, a prototypical opioid in the behavioral responses following the chronic constriction injury (CCI) model of neuropathic pain. Experiments were performed on eight groups (n=8) of male Sprague-Dawley rats (230-280 g). ⋯ Ethosuximide and morphine significantly decreased cold and mechano allodynia and thermal hyperalgesia. However, the co-administration of both drugs seems to be more effective than the ethosuximide or morphine alone on cold and mechano allodynia and thermal hyperalgesia. Our results suggest that ethosuximide block tactile and thermal hypersensitivity after the CCI model, also, ethosuximide potentiates the analgesic effects of morphine in neuropathic pain conditions and behavioral responses.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Jan 2012
Comparative StudyBlockade of microglial activation reduces mechanical allodynia in rats with compression of the trigeminal ganglion.
The present study investigated the role of microglia and p38 MAPK in the development of mechanical allodynia in rats with compression of the trigeminal ganglion. Male Sprague-Dawley rats weighing 250-260 g were used. Under pentobarbital sodium anesthesia, the animals were mounted onto a stereotaxic frame and given injections of 4% agar solution (10 μL) to compress the trigeminal ganglion. ⋯ Intracisternal administration of 100 μg of minocycline significantly inhibited both mechanical allodynia and activation of microglia produced by compression of the trigeminal ganglion. Intracisternal administration of 0.1, 1, or 10 μg of SB203580, a p38 MAPK inhibitor, also significantly decreased mechanical allodynia and p38 MAPK activation in the trigeminal ganglion-compressed group. These results suggest that activation of p38 MAPK in the microglia is an important step in the development of mechanical allodynia in rats with compression of the trigeminal ganglion and that the targeted blockade of microglial p38 MAPK pathway is a potentially important new treatment strategy for trigeminal neuralgia-like nociception.
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Matrix metalloproteinases (MMPs) have been implicated in the modulation of synaptic plasticity, glial activation, and long-term potentiation in the CNS. Here we demonstrate for the first time a mechanism for the regulation of nociceptive processing by spinal MMP-3 during peripheral inflammation. We first determined by western blotting that the catalytic (active) form of MMP-3 (cMMP-3) is increased in lumbar spinal cord following peripheral inflammation in rats. ⋯ The hypersensitivity behavior is prevented by intrathecal etanercept (TNF blockade). Treatment with cMMP-3 resulted in an increase in TNF release from spinal primary microglial, but not astrocyte cultures. These findings thus present direct evidence implicating MMP-3 in the coordination of spinal nociceptive processing via a spinal TNF-dependent mechanism.
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Oxaliplatin is an important drug used in the treatment of colorectal cancer. However, it frequently causes severe acute and chronic peripheral neuropathies. We recently reported that repeated administration of oxaliplatin induced cold hyperalgesia in the early phase and mechanical allodynia in the late phase in rats, and that oxalate derived from oxaliplatin is involved in the cold hyperalgesia. In the present study, we examined the effects of Ca²⁺ channel blockers on oxaliplatin-induced cold hyperalgesia in rats. ⋯ These data suggest that the L type Ca²⁺ channels/NFAT/TRPM8 pathway is a downstream mediator for oxaliplatin-induced cold hyperalgesia, and that Ca²⁺ channel blockers have prophylactic potential for acute neuropathy.