Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance
1 Department of Anesthesia, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China
2 Department of Anesthesiology and Perioperative Care, University of California, San Francisco, CA, 94143, USA
3 Department of Anesthesiology and Perioperative Care, University of California, San Francisco, CA, 94143, USA
4 Department of Anesthesia, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Str., Wangfujing Ave., Dongcheng District, Beijing, 100730, China
Molecular Pain 2012, 8:38 doi:10.1186/1744-8069-8-38Published: 21 May 2012
The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins) change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA) receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.