Pain
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Chronic pain can dominate all concerns for individuals suffering with it, leaving much of their time focused on trying to reduce pain rather than living their life, as they would most want to do, according to their values. The purpose of this study was to examine these processes, the degree of success patients have in following their values as guides for their actions, and relations between values-based action and other aspects of daily functioning. For this study we designed a brief inventory of patient values in domains of family, intimate relations, friends, work, health, and growth or learning. ⋯ Significant correlations of overall success with measures of avoidance and acceptance of pain supported the validity of scores from the values measure. Success in living according to values was correlated with measures of disability, depression, and pain-related anxiety. Regression analysis showed that success at living according to values predicted variance in functioning independent of acceptance of pain, supporting its incremental utility in a contextual analysis of chronic pain and its potential importance in treatment for chronic pain.
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Comparative Study
Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states.
Antisense (AS) oligodeoxynucleotides (ODNs) targeting the Nav 1.8 sodium channel have been reported to decrease inflammatory hyperalgesia and L5/L6 spinal nerve ligation-induced mechanical allodynia in rats. The present studies were conducted to further characterize Nav 1.8 AS antinociceptive profile in rats to better understand the role of Nav 1.8 in different pain states. Consistent with earlier reports, chronic intrathecal Nav 1.8 AS, but not mismatch (MM), ODN decreased TTX-resistant sodium current density (by 60.5+/-10.2% relative to MM; p<0.05) in neurons from L4 to L5 dorsal root ganglia and significantly attenuated mechanical allodynia following intraplantar complete Freund's adjuvant. ⋯ Finally, Nav 1.8 AS, but not MM, ODN treatment produced a small but significant attenuation of acute noxious mechanical sensitivity in naïve animals (17.6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states.
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Comparative Study
Contribution of the ventromedial hypothalamus to generation of the affective dimension of pain.
The ventromedial hypothalamus (VMH) is a core structure underlying the generation of affective behaviors to threats. The prototypical threat to an individual is exposure to a noxious stimulus and the dorsomedial division of the VMH (dmVMH) receives nociceptive input. The present study evaluated the contribution of the dmVMH to generation of the affective reaction to pain in rats. ⋯ These treatments did not alter thresholds of other tailshock elicited responses (vocalizations during tailshock or spinal motor reflexes). Bicuculline and muscimol administered into the dmVMH also elevated and lowered the asymptotic level of fear conditioning supported by dmVMH stimulation or tailshock. These findings demonstrate that the dmVMH contributes to the processing of pain affect and that the affective dimension of pain belongs to a broader class of sensory experience that represents threat to the individual.
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Important mechanisms that regulate inhibitory and facilitatory effects on TRPV1-mediated nociception are desensitization and phosphorylation, respectively. Using Ca2+-imaging, we have previously shown that desensitization of TRPV1 upon successive capsaicin applications was reversed by protein kinase C activation in dorsal root ganglion neurons and CHO cells. Here, using both Ca2+-imaging and patch-clamp methods, we show that PMA-induced activation of PKCepsilon is essential for increased sensitivity of desensitized TRPV1. ⋯ We also show that the expression level of PKCepsilon paralleled the amount of phosphorylated TRPV1 protein using an antibody specific for phosphorylated TRPV1 at S800. Furthermore, the anti-phosphoTRPV1 antibody detected phosphorylation of TRPV1 in mouse and rat DRG neurons and may be useful for research regarding nociception in native tissues. This study, therefore, identifies PKCepsilon and S800 as important therapeutic targets that may help regulate inhibitory effects on TRPV1 and hence its desensitization.
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Osteoarthritis (OA) is a debilitating disease in which primarily weight-bearing joints undergo progressive degeneration. Despite the widespread prevalence of OA in the adult population, very little is known about the factors responsible for the generation and maintenance of OA pain. Vasoactive intestinal peptide (VIP) was identified in the synovial fluid of arthritis patients nearly 20 years ago and the aim of this study was to examine whether VIP could be involved in the generation of OA pain. ⋯ Treatment of OA knees with a single injection of VIP6-28 diminished hindlimb incapacitance while increasing paw withdrawal threshold. This study showed for the first time that peripheral application of VIP causes increased knee joint allodynia and secondary hyperalgesia. Furthermore, antagonists that inhibit VIP activity may prove beneficial in the alleviation of OA pain.