Medical Pharmacology Chapter 13:  Pain Management:  Opioids

• Systemic Opioid Administration

   

  • Action at both supraspinal and spinal sites

    • Transmission of impulses, which as they reach consciousness will be interpreted as pain, begins with the activation of specific peripheral receptors called nociceptors by disease- or surgery-induced tissue injury. Nociceptors usually respond to high intensity, potentially damaging stimuli. Inflammatory processes often associated with disease or tissue trauma play a role in the initiation of nociception, mostly by sensitizing the nociceptors: which causes lowering of their activation threshold. Both A- and C-class nociceptors and their corresponding afferent fibers are the most important carriers of nociceptive stimuli from the skin, deep somatic structures, such as muscle and bone, and viscera. On going nociceptor-evoked discharges carried by these afferent fibers enter the spinal cord via the dorsal roots, extending into several ascending nociceptive pathways. The dorsal horn is not only a relay station for these signals, but also an area in which complex data integration of excitatory or inhibitory modulation occurs. courtesy of Roxane Pain Institute used with permission

       

  • Important opioid binding sites in descending pathways

    • The periaqueductal gray matter (PAG), periventral gray matter (PVG), and the nucleus raphe magnus (part of the rostroventral medulla) have high concentrations of opioid receptors, which are known to play an active role in the endogenous descending nociceptive control system. These pathways are serotonergic and selectively inhibit the STT, SRT, and SMT ascending pain tracts. Electrical stimulation of the PVG increases the response threshold to noxious stimuli. Several of the endogenous substances that are part of this control system and exhibit analgesic properties have been identified and include: β-endorphins (from the pituitary and basal hypothalamus) Enkephalin, and dynorphin. The latter two pain modulators appear to coexist in some areas of the dorsal horn where there is an abundance of opioid receptors in central terminals of primary afferents. courtesy of Roxane Pain Institute used with permission

    • Rostral ventral medulla

    • Locus ceruleus (see below)

    • Midbrain periaqueductal gray

  • Administration of exogenous opioids promotes release of endogenous opioids

     

    • Opioid Sites of Action

      Reticular formation (RF), vestibular nuclei (V), cerebellar roof nuclei (R), periaquiductal gray (PG).  Posterior hypothalamic nuclei (P), paraventricular hypothalamic nucleus (PV), substantia nigra (SN),  Thalamic nuclei (T), preoptic hypothalamic nuclei (PO), locus ceruleus (LC), median raphe nuclei (MR) .

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