Neurochemical Principles of Opioid Analgesia

Endogenous opioid peptides that occur naturally in the body and exogenous opiate alkaloids regulate nociceptive transmission at key points in the pain modulatory system.¹²¹Jessell TM, Kelly DD. Pain and analgesia. Principles of Neural Science, Third Edition, Kandel et al. editors, 1991, p.397

The mechanism of opioids

Modulation occurs through a combination of presynaptic and postsynaptic actions. Opioid receptors are located on the presynaptic terminals of nociceptive afferents as well as the dendrites of postsynaptic neurons.¹²²Jessell TM, Kelly DD. Pain and analgesia. Principles of Neural Science, Third Edition, Kandel et al. editors, 1991, p.397

Pharmacological studies indicate that opiates and opioid peptides regulate nociceptive transmission in part by inhibiting the release of glutamate, substance P, and other transmitters from the sensory neurons. ¹²³Jessell TM, Kelly DD. Pain and analgesia. Principles of Neural Science, Third Edition, Kandel et al. editors, 1991, p.397

At a cellular level, opioids decrease calcium ion entry resulting in a decrease in presynaptic neurotransmitter release. They also enhance potassium ion efflux from the post-synaptic neuron.¹²⁴Ballantyne JC, Fishman SM, Rathmell JP. Bonica’s Management of Pain, 2009, p1173 The efflux of potassium ions causes a build-up of negative charge. This hyperpolarization decreases the amplitude of the postsynaptic firing of the neuron, resulting in a decrease in signaling.¹²⁵Burt, AM. “Histology and Fine Structure of Nervous Tissue,” “Neuronal Communication,” and “Chemical Transmission.” In Textbook of Neuroanatomy. Philadelphia, PA: W. B. Saunders, Co., 1993