The journal of pain : official journal of the American Pain Society
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The facet joint is a common source of pain in both the neck and low back, and can be injured by abnormal loading of the spinal joints. Whereas a host of nociceptive changes including neuronal activation, neuropeptide expression, and inflammatory mediator responses has been reported for rat models of joint pain, no such responses have been explicitly investigated or quantified for painful mechanical injury to the facet joint. Two magnitudes of joint loading were separately imposed in a rat model of cervical facet joint distraction: Painful and nonpainful distractions. Behavioral outcomes were defined by assessing mechanical hyperalgesia in the shoulders and forepaws. Substance P (SP) mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7 following distraction. Painful distraction produced mechanical hyperalgesia that was significantly greater (P < .010) than that for a nonpainful distraction. Painful distraction significantly increased spinal SP mRNA (P = .048) and SP protein expression in the DRG (P = .013) at day 7 compared to nonpainful distraction. However, spinal SP protein for painful distraction was significantly less (P = .024) than that for nonpainful distraction at day 1. Joint distractions producing different behavioral outcomes modulate SP mRNA and protein in the DRG and spinal cord, suggesting that SP responses may be involved with different temporal responses in painful joint loading. ⋯ SP mRNA and protein in the DRG and spinal cord are quantified at 2 time points after cervical facet joint distractions that separately do or do not produce mechanical hyperalgesia. Studies describe a role for SP to contribute to pain produced by mechanical joint loading.
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We have recently shown that the prolongation of prostaglandin E2 hyperalgesia in a preclinical model of chronic pain-hyperalgesic priming-is mediated by release of cyclic adenosine monophosphate from isolectin B4-positive nociceptors and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn, acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously showed that antisense against an extracellular matrix molecule, versican, which defines the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation of prostaglandin E2 hyperalgesia. To further evaluate the mechanisms at the interface between the extracellular matrix and the nociceptor's plasma membrane involved in hyperalgesia prolongation, we interrupted a plasma membrane molecule involved in versican signaling, integrin β1, with an antisense oligodeoxynucleotide. Integrin β1 antisense eliminated mechanical hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine, in the primed rat. We also disrupted a molecular complex of signaling molecules that contains integrin β1, lipid rafts, with methyl-β-cyclodextrin, which attenuated the prolongation without affecting the acute phase of prostaglandin E2 hyperalgesia, while having no effect on cyclopentyladenosine hyperalgesia. Our findings help to define the plasma membrane mechanisms involved in a preclinical model of chronic pain. ⋯ The present study contributes to a further understanding of mechanisms involved in the organization of messengers at the plasma membrane that participate in the transition from acute to chronic pain.