Articles: hyperalgesia.
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Experimental glutamate and capsaicin-induced pain has not been described in tendon tissue despite the implications of addressing these receptors in pain management strategies. This study investigated pain induction and modulatory interactions by injecting glutamate (0.5 ml, 1 M) and capsaicin (0.5 ml, 5 microg, 33 microM) to human tendon tissue. Following the initial glutamate or capsaicin injection, a second injection of either glutamate (following capsaicin), capsaicin (following glutamate) or hypertonic saline (after both glutamate and capsaicin) was given. ⋯ The results indicate in tendon tissue a facilitation of response to capsaicin injection following glutamate injection. PPTs were only reliably reduced by capsaicin injection. These results emphasize the possible importance of peripheral glutamate receptor antagonists in pain management in musculoskeletal conditions.
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Intense stress and fear have long been known to give rise to a suppression of pain termed "stress-induced analgesia", mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of "stress-induced hyperalgesia", the neurobiological basis for this effect remains almost entirely unknown. ⋯ In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia.
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Chronic psychological stress is associated with visceral hyperalgesia and increased expression of spinal NK1 receptors (NK1Rs). We aimed to identify the role of spinal microglia in this process. ⋯ This is the first demonstration that stress-induced activation of spinal microglia has a key role in visceral hyperalgesia and associated spinal NK1R up-regulation.
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TNFalpha plays a pivotal role in rheumatoid arthritis (RA) but little is known of the mechanisms that link the inflammatory and nociceptive effects of TNFalpha. We have established a murine model of TNFalpha-induced TRPV1-dependent bilateral thermal hyperalgesia that then allowed us to identify distinct peripheral mechanisms involved in mediating TNFalpha-induced ipsilateral and contralateral hyperalgesia. Thermal hyperalgesia and inflammation were assessed in both hindpaws following unilateral intraplantar (i.pl.) TNFalpha. ⋯ However, TNFalpha-induced IL-1beta generation in both paws and the presence of local IL-1beta in the contralateral paw were essential for the development of bilateral hyperalgesia. These results identify a series of peripheral events through which TNFalpha triggers and maintains bilateral inflammatory pain. This potentially allows a better understanding of mechanisms involved in TNFalpha-dependent pain pathways in symmetrical diseases such as arthritis.
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Clin. Exp. Pharmacol. Physiol. · Apr 2009
Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.
1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. ⋯ The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.