Articles: hyperalgesia.
-
We performed a study on the antinociceptive effects of A1 and A2 type (A1LL and A2NTX, respectively) botulinum toxin on carrageenan-induced hyperalgesia in the rat. Both A1LL and A2NTX had antinociceptive effects in the carrageenan-induced inflammatory pain model, reducing the mechanical and thermal hyperalgesia. A2NTX also reduced the increase in c-fos immunoreactivity in L4-L5 spinal segments induced by carrageenan, suggesting that A2NTX inhibits the activation of spinal nociceptive afferent fibers that project to the CNS. Our results indicate that A2NTX may offer a new therapeutic tool to treat inflammatory pain.
-
Studies on the neuritis model suggest that in many patients with neuropathic pain, symptoms may be due to nerve inflammation rather than frank nerve injury. Treatments for these patients are often ineffective. The neuroprotective and hematopoietic agent erythropoietin (EPO) has been shown to reverse pain behaviors in nerve injury models and therefore may be of therapeutic benefit. ⋯ The levels of CCL2 and TNF-α mRNA in the nerve and Gelfoam were not significantly different following 120 μg/kg ARA290 treatment (n=3-7) compared to vehicle-treated animals (n=3-7; p=0.24; unpaired t tests). In summary, ARA290 may be beneficial in the treatment of neuropathic pain symptoms where signs of nerve injury are absent on clinical assessment. The mechanisms of action do not appear to involve the inhibition of TNF-α or CCL2 production.
-
In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice. ⋯ It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin.
-
Acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) are undesirable effects of opioids that have been reported in both animals and humans. However, the development of AOT and OIH in cases of potent, short-acting μ-opioid receptor agonist remifentanil administration remains controversial. It has been suggested that the emergence of AOT and OIH by remifentanil could be dose and infusion duration dependent, i.e., low dose and short infusions may lead to negative results. In this study, we determined whether AOT and OIH could be elicited by prolonged, continuous administration of remifentanil at maximally tolerable doses in C57BL/6 mice. ⋯ These results suggest that neither intra-infusion AOT nor postinfusion OIH develops in mice receiving continuous remifentanil when the possibility of cumulative tissue injury mimicking AOT or OIH is carefully avoided.
-
Regulator of G-protein signaling (RGS) proteins classically function as negative modulators of G-protein-coupled receptor signaling. In vitro, RGS proteins have been shown to inhibit signaling by agonists at the μ-opioid receptor, including morphine. The goal of the present study was to evaluate the contribution of endogenous RGS proteins to the antinociceptive effects of morphine and other opioid agonists. ⋯ In contrast, antinociception produced by either morphine or methadone was reduced in the tail-withdrawal test, a measure of spinal nociception. In whole-brain and spinal cord homogenates from mice expressing Gαo RGSi subunits, there was a small loss of Gαo expression and an accompanying decrease in basal G-protein activity. Our results strongly support a role for RGS proteins as negative regulators of opioid supraspinal antinociception and also reveal a potential novel function of RGS proteins as positive regulators of opioid spinal antinociceptive pathways.