Investigation of the effects of environmental enrichment in a rat model of neuropathic pain and related comorbidities: role of the endocannabinoid system

Chronic pain (CP) is a debilitating condition, with current treatments having limited efficacy and/or adverse effects. Environmental enrichment (EE) has consistently demonstrated beneficial effects on pain and mood, however its underlying mechanisms are essentially unexplored. The endocannabinoid system (ECS) plays a role in pain modulation and is influenced by EE. We therefore hypothesized that EE attenuates CP- and associated anxiodepressive-related behaviours in rats via the ECS. To test this hypothesis, we have: (i) characterized spontaneous behaviours in rats, particularly social interactions, in the context of EE, as well as the alterations induced by the spared nerve injury (SNI) neuropathy model; (ii) assessed the effects of different EE protocols on SNI-induced nociceptive and (iii) anxiodepressive behaviours in rats; and (iv) investigated ECS alterations in specific brain regions using HPLC-Mass Spectrometry and RT-qPCR. The results presented herein demonstrate that EE alleviated SNI-induced mechanical hypersensitivity regardless of its time of onset and duration, however, its anxiolytic and antidepressant effects were dependent on both factors. Moreover, EE mobilised endocannabinoids in a context- and sex-dependent manner. Pharmacological blockade of CB1 receptors confirmed that the antinociceptive, anxiolytic, and antidepressant effects of EE were mediated, at least in part, by CB1 receptor signalling. Additionally, SNI induced sex-specific changes in spontaneous behaviours, most notably in huddling. In conclusion, this thesis provides novel insights into the beneficial effects of EE in a rat model of neuropathic pain and its associated comorbidities, as well as the underlying mechanisms involved. Beyond its therapeutic potential, understanding the mechanisms by which EE mediates its beneficial effects may facilitate the development of novel therapeutic approaches. Moreover, the use of ethologically relevant behavioural measures strengthens the validity of the findings and enhances their translational value.

Funder

European Union

Publisher

University of Galway

Rights

CC BY-NC-ND

cbn

Collections

University of Galway Theses (PhD Theses)