Articles: hyperalgesia.
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There are sporadic reports that assorted combinations of B vitamins can alleviate pain in diabetic patients, but there is neither agreement on the relative efficacy of individual B vitamins nor understanding of the mechanisms involved. We therefore investigated the efficacy of a cocktail of the vitamins B1, B6 and B12 in alleviating behavioral indices of sensory dysfunction such as allodynia and hyperalgesia in diabetic rats and also the relative contribution of individual components of the cocktail. Repeated daily treatment with the cocktail of B vitamins for 7-9 days ameliorated tactile allodynia and formalin-evoked hyperalgesia in a dose-dependent manner and also improved sensory nerve conduction velocity in diabetic rats. ⋯ Only vitamin B6 improved sensory nerve conduction velocity slowing in diabetic rats when given alone. To address potential mechanisms of action, we measured markers of oxidative stress (lipid and protein oxidation) and inflammation (cyclooxygenase-2 (COX-2) and TNFalpha protein) in the nerve but treatment with the vitamin B cocktail did not significantly affect any of these parameters. The positive effects of B vitamins on functional and behavioral disorders of diabetic rats suggest a potential for use in treating painful diabetic neuropathy.
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Neuroscience letters · Jun 2009
Estrogen-dependent, sex-specific modulation of mustard oil-induced secondary thermal hyperalgesia by orphanin FQ in the rat.
Activation of opioid receptor-like 1 receptor (ORL(1)) by intrathecal administration of orphanin FQ (OFQ), an endogenous ligand for the ORL(1) receptor, has been shown to produce antinociception. In addition, we have recently shown gonadal hormone-dependent, sex-specific modulation of acute spinal nociception such that estrogen attenuated OFQ-induced antinociception in the female whereas testosterone was required for the expression of antinociception in the male. However, sex-related differences in the role of OFQ under hyperalgesic conditions are unknown. ⋯ Intrathecal administration of OFQ not only attenuated mustard oil-induced decrease in TFLs, i.e. reversed hyperalgesia, but also led to a significant increase in TFLs above the baseline, i.e. produced antinociception in male, OVX, and diestrous rats. However, OFQ failed to alter TFLs in proestrous or OVX+E females, thus these two groups with elevated estrogen levels remained hyperalgesic following mustard oil treatment. These findings demonstrate that OFQ modulates mustard oil-induced secondary hyperalgesia in an estrogen-dependent, sex-specific manner.
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We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [(3)H](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. ⋯ The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain.
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Korean J. Intern. Med. · Jun 2009
Effect of the combined use of tramadol and milnacipran on pain threshold in an animal model of fibromyalgia.
Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. ⋯ We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans.
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Comparative Study
Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder.
Females with Irritable Bowel Syndrome (IBS) and Temporomandibular Disorder (TMD) are characterized by enhanced sensitivity to experimental pain. One possible explanation for this observation is deficiencies in pain modulation systems such as Diffuse Noxious Inhibitory Control (DNIC). In a few studies that used brief stimuli, chronic pain patients demonstrate reduced DNIC. ⋯ Compared to controls, IBS and TMD patients reported an increased sensitivity to heat pain and failed to demonstrate pain inhibition due to DNIC. Controls showed a significant reduction in pain during the DNIC session. These findings support the idea that chronic pain patients are not only more pain sensitive but also demonstrate reduced pain inhibition by pain, possibly because of dysfunction of endogenous pain inhibition systems.