Is finding the common biological link(s) between pain and affect an infinity quest?

Abstract

Clinical studies have demonstrated comorbidity between painand depression or anxiety [1,2]. The prevalence of depression inpatientswithchronicpainreaches5–100%,theprevalenceofanxi-etydisorderreaches11–60%,andtheprevalenceofpaininpatientswithdepressiondisorderreaches15–100%dependingonthestudyand type of pain [3,4]. These comorbidities affect negatively thelife of the patients. It is still not clear whether there is a causalrelationship in the development of comorbidity between chronicpain and anxiety/depression or whether chronic pain and anxi-ety/depression have distinctly different mechanisms that coexistindependentofeachother.Thisquestionisnotonlyofconsiderableacademic interest but also of potential clinical importance whendevelopingtherapeuticinterventionsforthecomorbidchronicpainand affective disorder.Experimental animal studies have shown that chronic neuro-pathic pain is associated with structural and functional changes inbrain areas that are important for processing of emotions, such astheamygdala[5–8].Sincebrainareasimportantforemotionshavereciprocalconnectionswithpain-relaynucleiandplayaroleinreg-ulation of pain [9], it might be speculated that the functional andstructuralchangesintheseareasprovideacommonmechanismformaintenanceofpainandaffectchanges,suchasdepressionoranx-iety. In line with this proposal, some [5,10–12], but not all [13,14],studies with experimental animal models of chronic neuropathicpain have demonstrated co-occurrence of anxiety or depression,which, however, has varied depending on many factors. Amongthem are the age of the animals, the duration of the pathophysi-ological condition, and the type of affect studied [12]. Moreover,since genetic factors are known to influence both the developmentofchronicpain[15]andaffectivestates[16],itislikelythatgeneticfactors also play an important role in their comorbidity.Among potential common molecular and neurochemical linksbetween pain and anxiety is corticotropin-releasing factor (CRF)anditsCRF