Articles: hyperalgesia.
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J. Pharmacol. Exp. Ther. · May 2005
Comparative StudyAcetazolamide, a carbonic anhydrase inhibitor, reverses inflammation-induced thermal hyperalgesia in rats.
Inflammatory pain is linked to reduction in tissue pH. Tissue proton generation is mainly mediated by carbonic anhydrases (CAs). We therefore hypothesized that inhibition of CAs with acetazolamide (ACTZ) increases the tissue pH and reverses inflammation-induced pain. ⋯ Thus, the current data do not support our hypothesis that ACTZ reduces inflammatory hyperalgesia by raising the reduced pH in muscle. Although the possibility of pH changes and the role of CAs in the microenvironment cannot be ruled out, the mechanism of ACTZ-induced antihyperalgesia is not clear from this study. It is possible that the inhibition of ion channels and/or the inhibition of spinally located CAs contribute to the observed antihyperalgesia.
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The present study was undertaken to explore the role of gamma-aminobutyric acid transporters in the neuropathic pain. On the chronic constriction injury (CCI) rats 4 doses (5, 10, 20, 40 microg in group N5, N10, N20, N40, respectively) of specific gamma-aminobutyric acid transporter-1 inhibitor NO-711 or normal saline (in group NS) were intrathecally administered before sciatic nerve ligation (pre-treatment) or at the third day after ligation (post-treatment). The paw withdrawl latency (PWL) from a noxious thermal stimulus and paw withdrawl mechanical threshold (PWMT) of von Frey filament was used as measure of thermal hyperalgesia and tactile allodynia respectively. ⋯ NO-711 inhibited thermal hyperalgesia induced by CCI in a dose-dependent manner. Intrathecal pretreatment with different doses of NO-711 delayed the occurrence of thermal hyperalgesia, but could not delay the emergence of allodynia induced by CCI. This study indicates that gamma-aminobutyric acid transporter inhibitor has anti-thermal hyperalgesia and anti-tactile allodynia effects in neuropathic rats.
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Regulatory peptides · Apr 2005
Absence of diabetic hyperalgesia in bradykinin B1 receptor-knockout mice.
Experimental evidence has shown that the inducible bradykinin (BK) B1 receptor (BKB1-R) subtype is involved in the development of hyperalgesia associated with type 1 diabetes. Selective BKB1-R antagonists inhibited, whereas selective agonists increased the hyperalgesic activity in diabetic mice in thermal nociceptive tests. Here we evaluate the development of diabetic hyperalgesia in a BKB1-R-knockout (KO) genotype compared to wild-type (WT) mice. ⋯ The hyperalgesia observed in wild type mice was totally absent in the BKB1-R-KO mice. Furthermore, the selective BKB1-R agonist, desArg9BK, significantly increased the hyperalgesic activity in diabetic WT mice but had no effect on nociceptive responses in diabetic BKB1-R-KO mice. Taken together, the results confirm the crucial role of the BKB1-R, upregulated alongside inflammatory diabetes, in the development of diabetes-induced hyperalgesia.
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J. Pharmacol. Exp. Ther. · Apr 2005
Comparative StudyNociceptive sensitivity and opioid antinociception and antihyperalgesia in Freund's adjuvant-induced arthritic male and female rats.
The present study was designed to examine sex differences in complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia and sex differences in opioid antinociception and anti-hyperalgesia. Female rats developed inflammation and hyperalgesia faster and exhibited greater peak hyperalgesia than male rats. In arthritic (CFA-treated) rats, lower thresholds were observed during estrus and proestrus, and in nonarthritic (vehicle-treated) rats, lower thresholds were observed during proestrus. ⋯ Loperamide was more potent in male than female arthritic rats at producing antihyperalgesia. These data demonstrate sex differences in arthritis-induced hyperalgesia and responsiveness to opioid analgesics. In arthritic rats, the antinociceptive effects of opioid agonists are most probably mediated by both central and peripheral opioid receptors, whereas their antihyperalgesic effects are mediated primarily by actions at peripheral opioid receptors.
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Animal studies have established a role for the brainstem reticular formation, in particular the rostral ventromedial medulla (RVM), in the development and maintenance of central sensitisation and its clinical manifestation, secondary hyperalgesia. Similar evidence in humans is lacking, as neuroimaging studies have mainly focused on cortical changes. To fully characterise the supraspinal contributions to central sensitisation in humans, we used whole-brain functional magnetic resonance imaging at 3T, to record brain responses to punctate mechanical stimulation in an area of secondary hyperalgesia. ⋯ Brainstem activation was localised to two distinct areas of the midbrain reticular formation, in regions consistent with the location of nucleus cuneiformis (NCF) and rostral superior colliculi/periaqueductal gray (SC/PAG). The PAG and the NCF are the major sources of input to the RVM, and therefore in an ideal position to modulate its output. These results suggest that structures in the mesencephalic reticular formation, possibly the NCF and PAG, are involved in central sensitisation in humans.