Abstract
Rationale Pain reflects an integration of sensation, cognition, and affect, whereas chronic pain is associated with maladaptation. The cerebellum is increasingly recognised as a contributor to pain, especially towards affective-motivational facets, including relief-seeking from aversive experiences. Few have specifically investigated this, and much less in females, despite the notable prevalence of chronic pain in this population. Objectives To examine preference to seek cannabidiol- or oxycodone-analgesia, and cellular changes to the cerebellum in a female adolescent rat model of neuropathic pain. Methods We used a sciatic nerve chronic constriction injury (CCI) to model neuropathic pain in 6-week-old female rats and assessed thermal/mechanical nociception and anxiety-like behaviour. Preference for cannabidiol or oxycodone was quantified in a conditioned place preference paradigm. Immunostained and cleared cerebella were analysed for calbindin-positive Purkinje cells and parvalbumin-positive molecular layer interneurons within anterior (II–III, IV–V) and posterior (VI/Simplex, VII/Crus I) lobules. Results CCI evoked heat and cold allodynia, increased anxiety-like behaviour, and produced a place preference for cannabidiol and oxycodone. CCI resulted in minimal changes to calbindin-positive Purkinje cell or parvalbumin-positive interneuron density, however cannabidiol and oxycodone conditioning differentially modified cell density within the cerebellum of naïve and CCI animals. Conclusions Chronic neuropathic pain in female rats encourages seeking of cannabidiol and oxycodone, which may reflect ongoing affective disturbances. Cellular changes in the cerebellum were limited in this model of neuropathic pain, but unique cerebellar adaptations emerged following exposure to cannabidiol versus oxycodone. Further insight regarding cerebellar contributions to affective-motivational facets of chronic pain would be valuable.