Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Nov 2014
Effects of the calcium channel blockers Phα1β and ω-conotoxin MVIIA on capsaicin and acetic acid-induced visceral nociception in mice.
The effects of intrathecal administration of the toxins Phα1β and ω-conotoxin MVIIA were investigated in visceral nociception induced by an intraperitoneal injection of acetic acid and an intracolonic application of capsaicin. The pretreatments for 2h with the toxins reduced the number of writhes or nociceptive behaviors compared with the control mice. Phα1β administration resulted in an Imax of 84±6 and an ID50 of 12 (5-27), and ω-conotoxin MVIIA resulted in an Imax of 82±9 and an ID50 of 11 (4-35) in the contortions induced by the intraperitoneal injection of acetic acid. The administration of Phα1β resulted in an Imax of 64±4 and an ID50 of 18 (9-38), and ω-conotoxin MVIIA resulted in an Imax of 71±9 and an ID50 of 9 (1-83) in the contortions induced by intracolonic capsaicin administration. Phα1β (100/site) or ω-conotoxin MVIIA (30pmol/site) pretreatments caused a reduction in CSF glutamate release in mice intraperitoneally injected with acetic acid or treated with intracolonic capsaicin. The toxin pretreatments reduced the ROS levels induced by intraperitoneal acetic acid injection. Phα1β, but not ω-conotoxin MVIIA, reduced significantly the ROS levels induced by intracolonic capsaicin administration. ⋯ Phα1β is a ω-toxin with high therapeutic index and a broader action on calcium channels. It shows analgesic effect in several rodents' models of pain, including visceral pain, suggesting that this toxin has the potential to be used in clinical setting as a drug in the control of persistent pathological pain.
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Pharmacol. Biochem. Behav. · Nov 2014
Orexin A induced antinociception in the ventral tegmental area involves D1 and D2 receptors in the nucleus accumbens.
Previous studies have shown that there are functional interactions among the lateral hypothalamus (LH), ventral tegmental area (VTA) and the nucleus accumbens (NAc), implicating pain modulation in the central nervous system. It has been shown that the LH-VTA orexinergic projecting neurons play an important role in mediating the suppression of nociception in animal models. However, little is known about the function of intra-VTA orexin receptors and involvement of D1/D2 receptors within the NAc in this antinociception. ⋯ Our findings showed that intra-accumbal SCH-23390 and sulpiride dose-dependently prevented intra-VTA orexin-induced antinociception. Nevertheless, this effect is more potent in animals that received D2 receptor antagonist. It is supposed that orexin A can induce the antinociception through activation of orexinergic receptors which activate the dopaminergic inputs to the NAc in rats.
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Pharmacol. Biochem. Behav. · Nov 2014
Controlled Clinical Trial7 mg nicotine patch fails to enhance P300 neural indices of cognitive control among nonsmokers.
Nicotine administration facilitates and nicotine deprivation reduces cognitive control in smokers. Importantly, nicotine effects on cognition may reinforce smoking behavior, especially among individuals who have cognitive deficits. The target P300 (P3b) and distracter P300 (P3a) are well-validated electrocortical markers of attention- and memory-related cognitive control processes. ⋯ Nicotine did not enhance P3b or P3a amplitudes, nor did trait cognitive control moderate the influence of nicotine on these indices. Nicotine-induced changes in P3 amplitudes may be limited to nicotine deprivation and/or nonsmokers may be fundamentally different with respect to the influence of nicotine on P3b/P3a indices of cognitive control. Directions for future research that may further examine the effects of nicotine on P3b/P3a independent of withdrawal reversal are discussed.
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Pharmacol. Biochem. Behav. · Nov 2014
Establishment and characterization of an optimized mouse model of multiple sclerosis-induced neuropathic pain using behavioral, pharmacologic, histologic and immunohistochemical methods.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that causes debilitating central neuropathic pain in many patients. Although mouse models of experimental autoimmune encephalomyelitis (EAE) have provided insight on the pathobiology of MS-induced neuropathic pain, concurrent severe motor impairments confound quantitative assessment of pain behaviors over the disease course. To address this issue, we have established and characterized an optimized EAE-mouse model of MS-induced neuropathic pain. ⋯ Single bolus doses of amitriptyline (1-7mg/kg), gabapentin (10-50mg/kg) and morphine (0.1-2mg/kg) evoked dose-dependent analgesia in the bilateral hindpaws of EAE-mice; the corresponding ED50s were 1.5, 20 and 1mg/kg respectively. At day 39 p.i. in EAE-mice exhibiting mechanical allodynia in the hindpaws, there was marked demyelination and gliosis in the brain and lumbar spinal cord, mirroring these pathobiologic hallmark features of MS in humans. Our optimized EAE-mouse model of MS-associated neuropathic pain will be invaluable for future investigation of the pathobiology of MS-induced neuropathic pain and for efficacy profiling of novel molecules as potential new analgesics for improved relief of this condition.