Articles: hyperalgesia.
-
Br J Clin Pharmacol · Apr 2006
Randomized Controlled TrialHyperalgesia induced by cutaneous freeze injury for testing analgesics in healthy volunteers.
The early phases of the clinical development of new analgesic agents are severely hindered by a lack of reliable sensitive tests based on experimental pain models. The aim of this study was to assess the ability of a localized hyperalgesia model induced by cutaneous freeze injury to evaluate the pharmacodynamic profile of weak analgesic agents in healthy volunteers. ⋯ Cutaneous freeze injury coupled with a von Frey electronic device to assess the mechanical pain threshold is a convenient model that causes no discomfort. The improved sensitivity and stability of this experimental model of hyperalgesia over three consecutive days make it a useful tool for evaluating the efficacy and detecting the potential sites of action of analgesic agents such as nonsteroidal anti-inflammatory drugs in healthy human subjects.
-
Glial activation is known to contribute to pain hypersensitivity following spinal sensory nerve injury. In this study, we investigated mechanisms by which glial cell activation in medullary dorsal horn (MDH) would contribute to tactile hypersensitivity following inferior alveolar nerve and mental nerve transection (IAMNT). Activation of microglia and astrocytes was monitored at 2 h, 1, 3, 7, 14, 28, and 60 days using immunohistochemical analysis with OX-42 and GFAP antibodies, respectively. ⋯ There was no significant loss of trigeminal ganglion neurons by 28 days following IAMNT, suggesting that degenerative changes in central terminals of primary afferents might not contribute to glial activation. Minocycline, an inhibitor of microglial activation, reduced microglial activation, inhibited p38 mitogen-activated protein kinase (MAPK) activation in microglia, and significantly attenuated the development of pain hypersensitivity in this model. These results suggest that glial activation in MDH plays an important role in the development of neuropathic pain and activation of p38 MAPK in hyperactive microglia contributes to pain hypersensitivity in IAMNT model.
-
Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. ⋯ Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.
-
Comparative Study
Involvement of nociceptin/orphanin FQ and its receptor in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation.
The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous agonist of the N/OFQ peptide receptor (NOP receptor), has been demonstrated to be involved in many physiological and pathological functions including pain regulation. In the present study, the involvement of N/OFQ-NOP receptor system in electroacupuncture (EA)-produced anti-hyperalgesia was investigated in rats with peripheral inflammation. ⋯ Additionally, the combination of N/OFQ injection with EA treatment could enhance anti-hyperalgesia compared to that produced by each component alone. These findings suggested that the spinal N/OFQ-NOP system might be involved in EA analgesia, which may be one of the mechanisms underlying the anti-nociceptive effect of EA in rat's peripheral inflammatory pain.
-
Brain research bulletin · Mar 2006
Down-regulation of GFRalpha-1 expression by antisense oligodeoxynucleotide attenuates electroacupuncture analgesia on heat hyperalgesia in a rat model of neuropathic pain.
Glial cell line-derived neurotrophic factor (GDNF) has been proved to play an important role in the modulation of nociceptive transmission especially during neuropathic pain. It was reported that electroacupuncture (EA) had potent analgesic effect on neuropathic pain and our previous studies indicated that EA could activate endogenous GDNF signaling system (GDNF and its receptor GFRalpha-1) in dorsal root ganglions (DRGs) of neuropathic pain rats. ⋯ The results showed that: (1) cumulative EA had potent analgesic effect on neuropathic pain in rats; (2) the expression of GFRalpha-1 in DRGs was down-regulated by intrathecal delivery of antisense ODN, but not by normal saline (NS) or mismatch ODN; (3) EA analgesia was significantly attenuated by antisense ODN treatment. The present study demonstrated that endogenous GDNF signaling system was involved in EA analgesia on neuropathic pain in rats, which would deepen our realization of the mechanism of EA analgesia.