Behavioural brain research
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Classical behavioral tests in animal models of trigeminal neuropathic pain measure reflexive responses that are not necessarily measures of pain. To overcome the problem, we created a chronic constrictive nerve injury (CCI) rat model of pain by ligation of the infraorbital nerve (ION), and applied the orofacial operant test to assess behavioral responses to mechanical and cold stimulation in these rats. Animals were trained to voluntarily contact their facial region to a mechanical or a cold stimulation module in order to access sweetened milk as a positive reward. ⋯ Our orofacial operant test demonstrates mechanical allodynia, cold allodynia, and hyperalgesia in rats with chronic trigeminal nerve injury. The neuropathic pain in ION-CCI rats was partially alleviated by morphine. Thus, orofacial operant test provides a desirable behavioral assessment method for preclinical studies of chronic trigeminal neuropathic pain.
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Recently, environmental stimuli on different neurobiological events, via participation of distinct amygdalar (AMY) ORXergic fibers have aroused wide interests in view of their ability to modify neuronal linked stressful and physiological homeostatic conditions. Results of the present study indicate that ORXergic (ORX-A/B) circuits of the facultative hibernating golden hamster (Mesocricetus auratus) central AMY (CeA) and basolateral AMY (BlA) nuclei constitute major sites of feeding behaviors. Indeed, hamsters after treatment of BlA with ORX-A frequently ingested greater quantities of food as compared to controls, while ORX-B in CeA induced a very (p<0.001) great consumption of water. ⋯ When behavioral changes were compared to the expression of the specific ORXergic receptor (ORX-2R), an up-/down-regulating pattern was detected in some limbic areas (AMY, hippocampus and hypothalamus) following treatment with ORX-A or ORX-B plus NMDA. Overall, indications deriving from this study strongly point to hamster BlA-enriched ORX-A fibers in combination with either inhibitory or excitatory signals as main targets of hyperphagic responses while CeA ORX-B activities in presence of these same neuronal signals predominantly induced drinking motivational behaviors. The distinct behavioral activities of these two neuropeptides may have useful clinical bearings toward psychiatric and sleeping disorders such as bulimia and narcolepsy.
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p21-activated kinases (PAKs) are involved in signal cascades relevant for nociceptive processing and neuropathic pain. Particularly, the recently described group B PAKs 4, 5 and 6 regulate MAP-kinases and the rearrangement of the actin cytoskeleton, both of which have been linked to pain processing. However, a specific role of these PAKs in nociception has not yet been demonstrated. ⋯ However, the nociceptive response in formalin-induced paw inflammation was significantly reduced in knock-out mice associated with inhibition of MAP-kinase activation and a decreased number of formalin-induced c-Fos positive neurons in the spinal cord. Furthermore, in isolated neurons, we found a significantly reduced calcium response after stimulation of TRPA1-channels in PAK 5(-/-)- compared to PAK 5(+/+)-cells. Our results indicate that PAK 5 is involved in formalin-induced inflammatory nociception through regulation of MAPK-induced c-Fos-activation and formalin-specific TRP-channels.
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Central pathophysiological pathways of basal ganglia dysfunction imply a disturbed interaction of dopaminergic and cholinergic circuits. In Parkinson's disease imbalanced cholinergic hyperactivity prevails in the striatum. As recently shown intrastiatal botulinum neurotoxin A (BoNT-A) improves motor function in hemiparkinsonian rats. ⋯ Slight working memory deficits were observed in radial maze testing of both BoNT-A and sham injected animals arguing for a consequence of surgery rather than for a specific BoNT-A effect. In contrast, BoNT-A injected animals showed a reduced anxiety in open field and elevated plus maze compared to both sham-treated and naïve controls. As bilateral intrastriatal BoNT-A injections in normal rats do not cause cognitive impairments and reduce anxiety, and previous findings showed improvements of motor function in hemiparkinsonian rats following intrastriatal BoNT-A, it can be argued that intrastriatal BoNT-A could be a new therapeutic approach in Parkinson's disease.