Opioid pathophysiology

Kurz A, Sessler DI. Opioid-induced bowel dysfunction pathophysiology and potential new therapies. Drugs 2003 63 649-71. 

Currently, constitutive receptor activity and inverse agonism have been demonstrated for >40% of the known G protein coupled receptors [8]. Detailed current reviews are available concerning inverse agonism and constitutive activity in different G protein-coupled receptor systems [8-10]. The pathophysiological importance of inverse agonism has also been recently reviewed [8,9], The present review, on the other hand, will focus on constitutive activity and inverse agonism as they are manifested in the delta opioid receptor system. 

A woman with chronic cholestasis and disabling pruritus had severe but transient opioid withdrawal-like reactions after oral naltrexone 12.5 mg and 2 mg (18). This observation suggests the hypothesis that increased central opioidergic tone is a component of the pathophysiology of cholestasis. 

These agents have obvious therapeutic utility in the treatment of opioid overdose. As the understanding of the role of endogenous opioid systems in pathophysiological states e.g., shock, stroke, spinal cord and brain trauma) increases, additional therapeutic indications for these antagonists may develop. 

The pathophysiology of OIH is poorly understood. Various non-opioid chemicals, neurotransmitters, and receptors have been implicated, e.g., cholecystoki-nin (CCK), N-methyl D-aspartate (NMDA) receptor, neurokinin, etc. One mechanism for opioid-induced enhanced pain sensitivity may be the neuroplastic changes that result in part from the activation of descending pain facilitation mechanisms arising from the rostral ventromedial medulla (RVM) by increasing the activity of CCK in the RVM. These activated descending neural tracts facilitate nociceptive processing in the spinal cord. 

Figure 38.1. Clinical algorithm for differentiating worsening pain states despite continuation of opioid therapy. (Reprinted with permission from Mitra S. Opioid-induced hyperalgesia pathophysiology and clinical implications. J Opioid Manage 2008 4 123-130.)...

Mitra S. Opioid-induced hyperalgesia pathophysiology and clinical implications. / Opioid Manage 2008 4 123-130. 

A variety of genetic, pharmacoiogicai, and pathophysiological factors influence patient response to opioid anaigesics... 

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