IUPHAR review- Preclinical models of neuropathic pain: Evaluating multifunctional properties of natural cannabinoid receptors ligands.

Neuropathic pain remains prevalent and challenging to manage and is often comorbid with depression and anxiety. The new approach that simultaneously targets neuropathic pain and the associated comorbidities, such as depression and anxiety, is timely and critical, given the high prevalence and severity of neuropathic pain and the lack of effective analgesics. In this review, we focus on the animal models of neuropathic pain that researchers have used to investigate the analgesic effects of cannabidiol (CBD) and Beta-Caryophyllene (BCP) individually and in combination while addressing the impact of these compounds on the major comorbidity (e.g., depression, anxiety) associated with neuropathic pain. We also addressed the potential targets/mechanisms by which CBD and BCP produce analgesic effects in neuropathic pain models. The preclinical studies examined in this review support CBD and BCP individually and combined as potential alternative analgesics for neuropathic pain while showing beneficial effects on depression and anxiety.