Centrally mediated hyperalgesia

Distinguish between primary hyperalgesia and centrally mediated hyperalgesia... 

Centrally mediated hyperalgesia involves the hyperexcitability of second-order sensory neurons in the dorsal horn of the spinal cord. In the case of severe or persistent tissue injury, C fibers fire action potentials... 

OLDA possesses activity at TRPVl receptors with potency similar to that of capsaicin, and produces long-lasting nocifensive behavior and thermal hyperalgesia, which is blocked by TRPVl antagonists (Chu et al., 2003 Szolcsanyi et al., 2004 Walker et al., 2005). Therefore, OLDA may function as either a peripheral or central mediator of TRPVl activation. 

Despite intensive research on the neurobiological mechanisms of chronic pain, this therapeutic area remains one of the least satisfactorily covered by current drugs. There is considerable preclinical evidence that hyperalgesia and allody-nia following peripheral tissue or nerve injury is not only due to an increase in the sensitivity of primary afferent nociceptors at the site of injury but also depends on NMDA receptor-mediated central changes in synaptic excitabihty (Zieglgansberger and Tolle 1993 Sandkiihler and Liu 1998 Hide 2000 Parsons 2001 Fundytus 2001). 

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