Pain
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Pain catastrophizing has shown to predict avoidance behavior in acute and chronic pain, but the literature is inconsistent. The present study tested the hypothesis that current mood and threat context moderate the relationship between pain catastrophizing and performance duration. Affective-motivational models postulate that negative and positive moods provide information about whether an activity is respectively threatening or safe. ⋯ The opposite was found when participants experienced positive moods. Moreover, these relationships were most pronounced in a high threatening pain context. This study suggests that the relationship between pain catastrophizing and performance duration during painful activities is moderated by situational factors such as current mood and threat context.
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The fear-avoidance model advances fear of pain as a key factor in the origins of chronic pain disability. Initial evidence in those with chronic back pain reveals that exposure therapy reduces fear levels, disability, and pain. Despite the success of exposure in the clinic, fundamental research about its underlying mechanisms lags behind. ⋯ Results revealed that fear ratings for the CS+ were extinguished in the extinction group but not in the control group. Interestingly, omitting the ITI shocks not only reduced ITI startle responses in the context exposure group compared with the control group, but also reduced the fear ratings and startle responses elicited by the unpredictable CS. The clinical implications of these findings are discussed.
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Chronic compression (CCD) or dissociation of dorsal root ganglion (DRG) can induce cyclic adenosine monophosphate (cAMP)-dependent DRG neuronal hyperexcitability and behaviorally expressed hyperalgesia. Here, we report that protease-activated receptor 2 (PAR2) activation after CCD or dissociation mediates the increase of cAMP activity and protein kinase A (PKA) and cAMP-dependent hyperexcitability and hyperalgesia in rats. CCD and dissociation, as well as trypsin (a PAR2 activator) treatment, increased level of cAMP concentration, mRNA, and protein expression for PKA subunits PKA-RII and PKA-c and protein expression of PAR2, in addition to producing neuronal hyperexcitability and, in CCD rats, thermal hyperalgesia. ⋯ In addition, trypsin and PAR2 agonistic peptide-induced increase of cAMP was prevented by inhibition of PKC, but not Gαs. These findings suggest that PAR2 activation is critical to induction of nerve injury-induced neuronal hyperexcitability and cAMP-PKA activation. Inhibiting PAR2 activation may be a potential target for preventing/suppressing development of neuropathic pain.
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The NMDA and TRPV1 receptors that are expressed in sensory neurons have been independently demonstrated to play important roles in peripheral pain mechanisms. In the present study, we investigated whether the 2 receptor-channel systems form a functional complex that provides the basis for the development of mechanical hyperalgesia. In the masseter muscle, direct application of NMDA induced a time-dependent increase in mechanical sensitivity, which was significantly blocked when the muscle was pretreated with a specific TRPV1 antagonist, AMG9810. ⋯ Consistent with the biochemical data, the NMDA-induced mechanical hyperalgesia was also effectively blocked when the muscle was pretreated with a CaMKII or PKC inhibitor. Thus, NMDA receptors and TRPV1 functionally interact via CaMKII and PKC signaling cascades and contribute to mechanical hyperalgesia. These data offer novel mechanisms by which 2 ligand-gated channels in sensory neurons interact and reinforce the notion that TRPV1 functions as a signal integrator under pathological conditions.
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Glutamate is an essential transmitter in pain pathways. However, its broad usage in the central and peripheral nervous system prevents us from designing efficient glutamate-based pain therapies without causing harmful side effects. The discovery of vesicular glutamate transporters (VGLUT1-3) has been a crucial step in describing specific glutamatergic neuronal subpopulations and glutamate-dependent pain pathways. ⋯ The animals were less prone to develop an inflammatory-related state of pain and were, in the partial sciatic nerve ligation chronic pain model, much less hypersensitive to mechanical stimuli and did not develop cold allodynia or heat hyperalgesia. To take advantage of this neuropathic pain-resistant model, we analyzed Vglut2-dependent transcriptional changes in the dorsal spinal cord after nerve injury, which revealed several novel candidate target genes potentially relevant for the development of neuropathic pain therapeutics. Taken together, we conclude that VGLUT2 is a major mediator of nociception in primary afferents, implying that glutamate is the key somatosensory neurotransmitter.