Pain
-
Tactile acuity measured by 2-point discrimination performance is impaired in patients with complex regional pain syndrome type I (CRPS-I). This is mirrored by pain-associated shrinkage of the cortical representation of the affected limb. We investigated whether, also, more complex tactile performance assessed by a dynamic 2D-form perception task is disturbed in CRPS-I patients. ⋯ The performance in the BT was not impaired in CRPS-I patients (compared to sex- and age-matched controls from study I) and was not correlated to the TPDT. The intact 2D-form recognition ability in CRPS-I patients might be explained by intact dynamic tactile and proprioceptive functions, which appear to be uncompromised by the impaired static tactile perception, provided that the spacing of the dot pattern is above the individual tactile acuity. These intact 2D-form perception capacities may also be related to higher sensory integration functions like the visual system and intact semantic understanding, which may be spared by the cortical reorganization phenomena in CRPS-I.
-
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.
-
Lidocaine is clinically widely used as a local anesthetic inhibiting propagation of action potentials in peripheral nerve fibers. Correspondingly, the functional magnetic resonance imaging (fMRI) response in mouse brain to peripheral noxious input is largely suppressed by local lidocaine administered at doses used in a clinical setting. We observed, however, that local administration of lidocaine at doses 100 × lower than that used clinically led to a significantly increased sensitivity of mice to noxious forepaw stimulation as revealed by fMRI. ⋯ Additional experiments with nociceptor-specific CB(1) receptor knockout mice indicated an involvement of the CB(1) receptors located on the nociceptors. We conclude that low concentrations of lidocaine leads to a sensitization of the nociceptors through a CB(1) receptor-dependent process. This lidocaine-induced sensitization might contribute to postoperative hyperalgesia.
-
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.
-
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.