Chronic Pain and Substance Abuse
Chronic pain is frequently accompanied by a constellation of psychological characteristics, that may co-present as frank psychopathology. Several studies have shown the high co-morbidity of chronic pain, depression, anxiety, and/or somatization disorder.1-8 Given that: (1) chronic pain and psychological factors are co-morbid and reciprocally-interactive, and (2) unrecognized and/or untreated psychopathology may increase the experience of, and reactivity to (chronic) pain, then it becomes clear that the co-morbidity and putative relationship of these disorders must be considered in any meaningful paradigm for chronic pain management.
Substance Abuse as Bio-psychological Co-morbidity
While considerable research has focused upon particular psychological disorders (e.g., depression, anxiety) that are co-morbid to chronic pain, it is equally important to consider the evident problem of substance abuse (and addiction) in this light, given the noted prevalence of pain, psychologic and substance abuse disorders, and the growing body of evidence to support the putative relationship of these disorders. The abuse of controlled substances among chronic pain patients is common, and is a significant epidemiological problem that exacerbates the impact of chronic pain and psychological conditions, and thus imposes further burdens, if not impediments, upon practical pain management.9-11
By definition, chronic pain is both a physiologic and psychological event, and we have posited that chronic pain and particular Axis I psychological disorders (e.g., depression, anxiety, somatization and substance abuse) have common underlying substrates.12 But such substrates are not invariably expressed; we believe that this correlation of chronic pain, emotional reactivity, and substance abuse demonstrate the interplay of genetic, phenotypic, and environmental-situational factors occurring as a spectrum disorder.12-15
On the biological level, several genetic (e.g., serotonin transporter gene) molecular (e.g., variants of the serotonin transporter, 5-HTT(LPR)); neuropharmacologic (e.g., serotonin, norepinephrine, dopamine, glutamate, opiate); and neuroanatomical systems (e.g., orbital cortex, cingulate, and central and medial divisions of the amygdala) are common to these disorders.16-18 We have raised the possibility that in pain spectrum disorders, the neural and/or glial function, and/or (micro/macro) anatomy of brain networks mediating noxious sensation and perception(s)—as well as those involved in cognitive and emotive dimensions of reinforcement and/or reward—in some way become disrupted or dysfunctional. Genetic variation(s) could predispose the expression of phenotypes for neural and/or glial function to alter the network properties and activity pattern(s) within brain systems to elicit the differential presentation of various features along a pathologic continuum (i.e.- a spectrum of chronic pain, depression, somatization and/or substance abuse).19 The affective components of chronic pain are similar (if not identical) to those of mood disorder with somatic features.20 We have posited that “…particular individuals have a pre-disposition to…neural sensitization within these pathways, as a consequence of over-reactivity to insult and trauma, inflammation, or aberrant response to environmental input(s)… [this] might induce pathologic patterns of sensory (hyper)reactivity, altered cognitive processing and emotional responses, and loss of impulse control. In this way, persistent pain, psychopathology, and substance abuse may be correlated and reflect related mechanistic processes…”.21 In this way, psychopathology (including substance abuse) can be seen as an aberrant responsiveness of the peripheral and central nervous system. Koob and LeMoal claim that this could establish “…addiction [as] a type of chronic pain syndrome characterized by emotional pain, dyshporia…and interpersonal difficulties… [for which certain] …drugs can be…self-medication.”22
Evidence for a Genetic Basis?
Chromosomal quantitative trait loci (QTL) have been identified for alleles that affect neural phenotypes that may be involved in the (co-)predisposition to, and co-expression of pain, certain psycho-pathologies, and substance abuse.23 The phenotypes for pain, psychopathology, and substance abuse are multi-factorial,24,25 and it is probable that phenotypic expression occurs along a continuum that is dependent upon influences within the CNS microenvironment incurred by interactions between internal and external environment(s)—both during critical developmental periods, as well as throughout the lifespan.26 Thus, it may be that genotypic variants might pre-dispose either a somewhat ‘generalized’ pattern of susceptibility in which neural substrates of (internal and external) environmental sensitivity, reinforcement, and reward are altered to affect interpretive/associative aspects of bodily sensations (including discomfort and pain), and emotionality, or a more ‘focal’ diathesis in which particular neural phenotypes directly correlate to certain forms of pain and/or psycho-pathology and substance abuse. In this model, genetically-influenced expression of neurotransmitters, their receptors and transporters, intracellular signaling molecules and/or ion channels may underlie development of particular types of pain, somatic and cognitive features of depression, somatization, and decreased opioid neuromodulation. This would thus reinforce a need for higher doses of opioids and an enhanced potential for misuse/abuse.27,28
…Or Evidence Biased?
Interpretations of these findings may actually incur bias about the relative importance of genetic influences. Such studies emphasize genetics (and “down-stream” biological effects) over environmental factors and, in this way, impart a deterministic perspective. At face value, one could argue that such a bias might be beneficial, in that it grounds chronic pain and substance abuse to a disease-model, and hence establishes this as ‘beyond the patient’s control or discretion,’ and thereby fortifies the obligation for medical treatment.
However, a problem with such a reductionist viewpoint is that it evaluates only the influence of genes or environment, does not sufficiently account for interaction and synergy among and between variables and, as a result, may foster a “one size fits all” approach to intervention and treatment. This type of over-simplification is implicit to many genetic studies of pain. Without adequate consideration of integrated bio-psychosocial variables, conclusions may err so as to emphasize a genetic determinism or, at the other extreme, the purely psychosocial effects of environment.29