Opioids, Pain, the Brain, and Hyperkatifeia: A Framework for the Rational Use of Opioids for Pain

Abstract

Objective Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. Results In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek “katifeia” for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Conclusions Repeated engagement of opponent processes without time for the brain’s emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement

“…Furthermore, L822429 did not affect mechanical hypersensitivity (a model of hyperalgesia) observed in heroin self-administering rats. Hyperalgesia has been proposed as another component of negative emotional states that may drive the transition to opioid addiction (Shurman et al, 2010). Taken together, these observations argue against a specific role for the SP/NK1R system in the recruitment of negative emotionality that contributes to the escalation of heroin self-administration, although the SP/ NK1R system may be engaged early on in the neuroadaptations associated with initial opioid self-administration.…”

Dynamic risk factors in the misuse of opioid analgesics

“…In addition, mental disorders that have an increased risk of substance abuse include dissociative disorders [63], schizophrenia [64], and bipolar disorders [65,66]; depression [67,68], borderline personality disorder [66,69], suicidal ideation [67,70], post-traumatic stress disorder [30], gambling addiction [71], panic and anxiety disorders [72,73], body dysmorphic disorder [74], social phobia and agoraphobia [75], and a recently described state of emotional distress known as hyperkatifeia [76]. In a study (n=288) of outpatients on chronic opioid therapy for pain of various etiologies, a history of psychiatric disorders was associated with an elevated risk for opioid misuse [32].…”

Opioids

“…The analgesic effects of opioids are caused by direct inhibition of nociceptive activity that ascends from the dorsal horn of the spinal cord to the brain circuitry associated with pain and also by activation of pain control circuits that descend from the midbrain via the rostral ventromedial medulla to the dorsal horn of the spinal cord. Endogenous opioid peptides and their receptors are highly localized to both the ascending and descending pain control circuits (Figure 5.12; for further reading, see Shurman et al, 2010).…”