The Journal of neuroscience : the official journal of the Society for Neuroscience
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Comparative Study
Bradykinin and nerve growth factor play pivotal roles in muscular mechanical hyperalgesia after exercise (delayed-onset muscle soreness).
Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes delayed-onset muscle soreness (DOMS), a kind of muscular mechanical hyperalgesia. The substances that induce this phenomenon are largely unknown. Peculiarly, DOMS is not perceived during and shortly after exercise, but rather is first perceived after approximately 1 d. ⋯ We also showed that rat NGF sensitized thin-fiber afferents to mechanical stimulation in the periphery after 10-20 min. Thus, NGF upregulation through activation of B(2) bradykinin receptors is essential (though not satisfactory) to mechanical hyperalgesia after exercise. The present observations explain why DOMS occurs with a delay, and why lengthening contraction but not shortening contraction induces DOMS.
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Striatal dopamine (DA) and acetylcholine (ACh) regulate motivated behaviors and striatal plasticity. Interactions between these neurotransmitters may be important, through synchronous changes in parent neuron activities and reciprocal presynaptic regulation of release. How DA signaling is regulated by striatal muscarinic receptors (mAChRs) is unresolved; contradictory reports indicate suppression or facilitation, implicating several mAChR subtypes on various neurons. ⋯ In nucleus accumbens (NAc) core or shell, mAChR function was prevented in M(4)-knock-outs, but not M(2)- or M(5)-knock-outs. These data indicate that striatal mAChRs, by inhibiting ACh release from cholinergic interneurons and thus modifying nAChR activity, offer variable control of DA release probability that promotes how DA release reflects activation of dopaminergic axons. Furthermore, different coupling of striatal M(2)/M(4)-mAChRs to the control of DA release in CPu versus NAc suggests targets to influence DA/ACh function differentially between striatal domains.
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The inflammatory response is thought to contribute to secondary damage after spinal cord injury (SCI). Polyunsaturated fatty acids (PUFAs) play an important role in the onset and resolution of inflammation. Arachidonic acid (AA), an omega-6 PUFA, contributes to the initiation of inflammatory responses, whereas docosahexaenoic acid (DHA), an omega-3 PUFA, has antiinflammatory effects. ⋯ These results demonstrate that fenretinide treatment after SCI can reduce inflammation and tissue damage in the spinal cord and improve locomotor recovery. These beneficial effects may be mediated via the ability of fenretinide to modulate PUFA homeostasis. Since fenretinide is currently in clinical trials for the treatment of cancers, this drug might be a good candidate for the treatment of acute SCI in humans.