Due to its localization at multiple key structures in central and peripheral pain pathways, mGluR5 plays a role in the development and expression of neuropathic pain. In addition, following nerve injury or inflammation, mGluR5 overexpression has been observed in both central (spinal cord, brainstem) and peripheral (trigeminal and dorsal root ganglia, primary afferent terminals) components of pain pathways, further amplifying nociceptive signaling and contributing to pain hypersensitivity.

Basimglurant is a mGluR5 negative allosteric modulator (NAM) with high selectivity (>1000-fold vs other mGluRs), high affinity to intracellular mGluR5 and is the most potent of NAMs tested on intracellular mGluR5 in neuron cultures.

Basimglurant (0.1-10 mg/kg SC or PO) was tested in well-established rodent models of neuropathic / chronic pain: chronic constriction nerve injury in rats (Bennett model), spinal nerve ligation in rats (Chung model), and formalin-induced pain in mice.

• Bennett model: total foot withdrawals from a cold bath were measured before and after basimglurant or vehicle.
• Chung model: mechanical allodynia and thermal hyperalgesia were measured.

Beneficial effects of basimglurant on response to pain inducing stimuli were observed in all models:

• Bennett model: inhibited cold allodynia, up to 58% at highest dose.
• Chung model: decreased mechanical sensitivity, with highest dose restoring paw withdrawal thresholds to pre-injury levels, indicating near total anti-allodynic efficacy.
• Formalin model: dose-dependently reduced paw licking in the late phase.