Spinal mechanisms of pain, hyperalgesia and modulation by anesthetics.

摘要

We have focused on rat and mouse spinal dorsal horn neuronal (DHN) response modulation by inflammation (disc herniation), anesthesia and the irritant mustard oil (MO). Studies suggest that local inflammatory reaction caused by herniated nucleus pulposus (NP) plays a key role in disc herniation-induced radiculopathy. We therefore hypothesized that NP applied to the fifth lumbar (L5) dorsal root ganglion (DRG), in the absence of a mechanical compression, would enhance the responses of DHN's that signal both noxious and non-noxious stimuli (WDR neurons). This was tested in a rat model by recording from single lumbar DHN's while stimulating the corresponding receptive field area. Responses were recorded before, and for several hours after, the application of autologous NP to the L5 DRG. A significant and rapid enhancement of responses to both non-noxious and noxious touch, as well as to noxious heat, was found in this study. Blockade of the action of tumor necrosis factor alpha (TNF-alpha) by the co-application of a soluble TNF-alpha receptor significantly reduced these effects. Thus, TNF-alpha is involved in NP-induced DHN sensitization. In a separate study an enhancement of windup following application of NP was observed, supporting a central sensitizing effect of NP.;In addition to our investigations of the sensitizing effects of NP on DHN's, we studied the effects of MO applied topically to the skin on DHN responses. We observed that mustard oil applied topically causes cross-sensitization to thermal stimuli but self-desensitization to repeated application.;The site at which gas anesthetics act to produce immobility remain incompletely understood. We studied the effects of halothane and isoflurane on spinal DHN windup under concentrations which bracket that required to produce immobility. Windup was utilized because it may reflect temporal summation of pain sensation and behavioral responses. Halothane suppressed windup, whereas isoflurane suppressed general neuronal excitability, but enhanced windup. Halothane may suppress movement in response to a noxious stimulation by acting within the dorsal horn to reduce incoming sensory information, whereas isoflurane may act at a different site, such as within the ventral horn to more directly suppress movement.