Pain
-
The most obvious impairments associated with spinal cord injury (SCI) are loss of sensation and motor control. However, many subjects with SCI also develop persistent neuropathic pain below the injury which is often severe, debilitating and refractory to treatment. The underlying mechanisms of persistent neuropathic SCI pain remain poorly understood. ⋯ The amount of S1 reorganization in subjects with SCI significantly correlated with on-going pain intensity levels. This study provides evidence of a link between the degree of cortical reorganization and the intensity of persistent neuropathic pain following SCI. Strategies aimed at reversing somatosensory cortical reorganization may have therapeutic potential in central neuropathic pain.
-
Studies in animals and humans suggest that neonatal and early infant pain or stress experiences can induce long-term alterations in somatosensory and pain processing. We studied pain and sensory sensitivity in school-aged children (9-16 years) who had suffered moderate (N=24) or severe (N=24) burn injuries in infancy (6-24 months of age) and 24 controls. Quantitative sensory testing entailing detection and pain thresholds for thermal and mechanical stimuli and perceptual sensitization to tonic heat and repetitive mechanical stimuli was performed. ⋯ In these children, mechanical pain sensitivity and detection thresholds were not consistently altered. This differential pattern of altered sensory and pain sensitivity may reflect differences in experienced stress, pain and analgesic treatment between moderately and severely burned children. Most importantly, our findings suggest that early traumatic and painful injuries, such as burns, can induce global, long-term alterations in sensory and pain processing.
-
Activation of P2X3,2/3 receptors by endogenous ATP contributes to the development of inflammatory hyperalgesia. Given the clinical importance of mechanical hyperalgesia in inflammatory states, we hypothesized that the activation of P2X3,2/3 receptors by endogenous ATP contributes to carrageenan-induced mechanical hyperalgesia and that this contribution is mediated by an indirect and/or a direct sensitization of the primary afferent nociceptors. Co-administration of the selective P2X3,2/3 receptors antagonist A-317491, or the non-selective P2X3 receptor antagonist, TNP-ATP, with carrageenan blocked the mechanical hyperalgesia induced by carrageenan, and significantly reduced the increased concentration of tumor necrosis factor alpha (TNF-alpha) and chemokine-induced chemoattractant-1 (CINC-1) but not of interleukin-1 beta (IL-1 beta) induced by carrageenan. ⋯ Intrathecal administration of oligonucleotides antisense against P2X3 receptors for seven days significantly reduced the expression of P2X3 receptors in the saphenous nerve and significantly reduced the mechanical hyperalgesia induced by carrageenan. We concluded that the activation of P2X3,2/3 receptors by endogenous ATP is essential to the development of the mechanical hyperalgesia induced by carrageenan. Furthermore, we showed that this essential role of P2X3,2/3 receptors in the development of carrageenan-induced mechanical hyperalgesia is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of TNF-alpha and by a direct sensitization of the primary afferent nociceptors.
-
TrpV1, the receptor for capsaicin, contributes to nociception in animals but appears to be much more important for signaling increased behavioral sensitivity in the injured state. The current study examined the relationship between the marked reduction in heat hyperalgesia after incision in TrpV1 knockout (KO) mice and the activity of the nociceptors in these same mice. Also, the role of TrpV1 in spontaneous activity (SA) of afferents after incision was examined. ⋯ We conclude that a distinct class of afferents outside the mechano-heat-sensitive afferent population likely contributes to heat hypersensitivity after plantar incision. KO of TrpV1 influences SA in these unclassified afferents in incised skin. SA in these afferents is perhaps a manifestation of heat sensitization.