汕头大学医学院药理学精品课程 Analgesic Drugs.pptVIP

Analgesic Drugs Department of Pharmacology Zhang Yan-mei Mechanisms of Pain and Nociception Nociception is the mechanism whereby noxious peripheral stimuli are transmitted to the central nervous system. Pain is a subjective experience, not always associated with nociception. Mechanisms of Pain and Nociception Polymodal nociceptors (PMN) are the main type of peripheral sensory neuron that responds to noxious stimuli. The majority are non-myelinated C-fibres whose endings respond to thermal, mechanical and chemical stimuli. Mechanisms of Pain and Nociception Chemical stimuli acting on PMN to cause pain include bradykinin, 5-HT, and capsaicin. PMN are sensitised by prostaglandins, which explains the analgesic effect of aspirin-like drugs, particularly in the presence of inflammation. Nociceptive fibres terminate in the superficial layers of the dorsal horn, forming synaptic connections with transmission neurons running to the thalamus. Mechanisms of Pain and Nociception PMN neurons release glutamate (fast transmitter) and various peptides (especially substance P) which act as slow transmitters. Peptides are also released peripherally and contribute to neurogenic inflammation. Neuropathic pain, associated with damage to neurons of the nociceptive pathway rather than an excessive peripheral stimulus, is frequently a component of chronic pain states, and may respond poorly to opioid analgesics. Modulation of Pain Transmission Transmission in the dorsal horn is subject to various modulatory influences, constituting the ‘gate control’ mechanism. Descending pathways from the midbrain and brainstem exert a strong inhibitory effect on dorsal horn transmission. Electrical stimulation of the midbrain periaqueductal grey (PAG) causes analgesia through this mechanism. Modulation of Pain Transmission The descending inhibition is mediated mainly by enkephalins, 5-HT, noradrenaline and adenosine. Opioids cause analgesia partly by activating these descending pathways, partly by inhib