Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification

Abstract

There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs.

Perspective: This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs.

Keywords: Overlapping conditions; classification; diagnosis; genetic factors; pain sensitivity; psychological factors.

Figure 1

Questions about pain asked in the 2009 National Health Interview Survey.

Figure 2

Venn diagram depicting overlap of jaw/face pain and other painful conditions, US adults, 2009. Source: the authors’ analysis of the 2009 National Health Interview Survey.

Figure 3

Sociodemographic distribution of 4 pain conditions in US adults, 2009. Source: the authors’ analysis of the 2009 National Health Interview Survey.

Figure 4

This model depicts likely determinants that contribute to the risk of onset and maintenance of common chronic overlapping pain conditions (COPCs). These factors are determined by genetic variability and environmental events that determine an individual’s psychological profile and pain amplification status. These 2 primary domains are interactive and influence the risk of pain onset and persistence. Likely modifiers of the interaction between genetic and environmental factors include sex and ethnicity. Abbreviations: MAO, monoamine oxidase; GAD65, glutamate decarboxylase; NMDA, N-Methyl-D-aspartic acid; CREB1, CAMP responsive element binding protein 1; GR, glucocorticoid receptor; CACNA1, calcium channel, voltage-dependent, T type, alpha 1I subunit; POMC, proopiomelanocortin; NET, norepinephrine transporter; BDNF, brain-derived neurotrophic factor; NGF, nerve growth factor; IKK, IκB kinase; COMT, catechol-O-methyl transferase.