Endogenous Analgesia, Dependence, and Latent Pain Sensitization

摘要: Endogenous activation of µ-opioid receptors (MORs) provides relief from acute pain. Recent studies have established that tissue inflammation produces latent pain sensitization (LS) is masked by spinal MOR signaling for months, even after complete recovery injury and re-establishment normal thresholds. Disruption with inverse agonists reinstates precipitates cellular, somatic, aversive signs physical withdrawal; this phenomenon requires N-methyl-d-aspartate receptor-mediated calcium-sensitive adenylyl cyclase type 1 (AC1). In review, we present a new conceptual model the transition to chronic pain, based on delicate balance between LS endogenous analgesia develops painful injury. First, activates pathways. Second, cord establishes constitutive activity (MORCA) as it attempts control Third, over time, body becomes dependent MORCA, which paradoxically sensitizes Stress or escalates opposing inhibitory excitatory influences nociceptive processing pathological consequence increased opioid tone. Pain begets MORCA vulnerability in vicious cycle. The final result silent insidious state characterized escalation two transmission: mediated AC1 (which maintains accelerator) inhibition brake). This raises prospect homeostatic interactions NMDAR–AC1-mediated creates lasting develop Thus, syndromes may failure MORs loss analgesic control. An overarching long-term therapeutic goal future research alleviate either (a) facilitating analgesia, thus restricting within remission, (b) extinguishing altogether.