Advances in psychosomatic medicine
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Addictive drugs have in common that they are voluntarily self-administered by laboratory animals (usually avidly), and that they enhance the functioning of the reward circuitry of the brain (producing the 'high' that the drug user seeks). The core reward circuitry consists of an 'in-series' circuit linking the ventral tegmental area, nucleus accumbens and ventral pallidum via the medial forebrain bundle. Although originally believed to simply encode the set point of hedonic tone, these circuits are now believed to be functionally far more complex, also encoding attention, expectancy of reward, disconfirmation of reward expectancy, and incentive motivation. 'Hedonic dysregulation' within these circuits may lead to addiction. ⋯ Stress-triggered relapse involves (a) the central nucleus of the amygdala, the bed nucleus of the stria terminalis, and the neurotransmitter corticotrophin-releasing factor, and (b) the lateral tegmental noradrenergic nuclei of the brain stem and the neurotransmitter norepinephrine. Cue-triggered relapse involves the basolateral nucleus of the amygdala, the hippocampus and the neurotransmitter glutamate. Knowledge of the neuroanatomy, neurophysiology, neurochemistry and neuropharmacology of addictive drug action in the brain is currently producing a variety of strategies for pharmacotherapeutic treatment of drug addiction, some of which appear promising.
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Ketamine is an N-methyl-D-aspartate receptor antagonist that has been in clinical use in the USA for over 30 years. Its ability to provide profound analgesia and amnesia while maintaining spontaneous respiration makes it an ideal medication for procedure-related pain and trauma. In the chronic pain arena, its use continues to evolve. ⋯ Its potential ability to prevent 'windup' and, possibly, 'reboot' aberrant neurologic pathways in neuropathic and central pain states has generated intense interest. However, the long-term use of ketamine for chronic neuropathic pain is limited by its side effect profile, and is largely anecdotal. More research is needed to better ascertain its long-term efficacy and side effects, to determine the ideal candidates for sustained treatment and to develop means of exploiting the antinociceptive properties of ketamine while minimizing the adverse effects.
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Chronic opioid therapy for patients with chronic noncancer pain has become controversial, given the rising prevalence of opioid abuse. The prevailing literature suggests that the rate of addiction in chronic noncancer pain patients exposed to opioid therapy is relatively low, especially in those patients without significant concomitant psychiatric disorders and personal and family history of addiction. However, the escalating rate of misuse of prescription opioids has resulted in many clinicians caring for these patients to be more judicious in prescribing opioids. ⋯ Managing the patient with pain and co-occurring opioid abuse is equally challenging. Diagnostic issues, current guidelines for the appropriate use of opioids in the chronic pain population and risk stratification models are examined. Pharmacologic and nonpharmacologic treatment strategies for the patient with pain and opioid addiction are reviewed.