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524458 
Journal Article 
Peripheral mechanisms of opioid analgesia 
Stein, C; Lang, LJ 
2009 
Yes 
Current Opinion in Pharmacology
ISSN: 1471-4892 
9 
1 
3-8 
English 
Potent and clinically significant analgesic effects can be brought about by opioids acting outside the central nervous system. Injury and inflammation of peripheral tissues leads to increased synthesis, axonal transport, membrane-directed trafficking and G-protein coupling of opioid receptors in dorsal root ganglion neurons. These events are dependent on neuronal electrical activity, cytokines and nerve growth factor and lead to an enhanced analgesic efficacy of peripherally active opioids. Leukocytes infiltrating inflamed tissue upregulate signal-sequence-encoding mRNA for beta-endorphin and its processing enzymes. Depending on the cell type and stimulus, the opioid release is contingent on extracellular Ca2+ or on release of Ca2+ from endoplasmic reticulum. Analgesia results from inhibition of sensory neuron excitability and of proinflammatory neuropeptide release. 
dorsal-root ganglia; inflammatory pain; beta-endorphin; neuropathic; pain; polymorphonuclear cells; containing leukocytes; activation; triggers; adhesion molecule-1; sensory neurons; rat model