Animal models of
drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of
corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to
opiates often leads to the development of mechanical
hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to
heroin or
cocaine self-administration, or in rats made dependent on
ethanol via
ethanol vapor exposure (
ethanol-dependent group). In
heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering
cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to
heroin LgA rats,
ethanol-dependent rats also developed mechanical
hypersensitivity after eight weeks of
ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the
hypersensitivity observed in rats dependent on
heroin or
ethanol. The emergence of mechanical
hypersensitivity with
heroin and
ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and
pain-related states may provide insight into mechanisms underlying the transition to
drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled '
Post-Traumatic Stress Disorder'.