Statins: Do They Aggravate or Ameliorate Neuropathic Pain?

• Clinical studies suggest statins have neuropathic pain–inducing effects.
• Cholesterol-lowering actions may contribute to neuropathic pain induction.
• Preclinical studies suggest neuropathic pain–attenuating effects of statins.
• Cholesterol-independent antiinflammatory actions of statins may attenuate neuropathy.
• Experimental studies are needed to understand the dual role of statins.

Neuropathic pain is a debilitating condition caused by a lesion or disease of the somatosensory nervous system. Statins inhibit the rate-limiting step in cholesterol biosynthesis by blocking 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Apart from the cholesterol-reducing actions of statins, recent studies have shown their pleiotropic actions; accordingly, their usefulness in attenuating different disease states has been described in preclinical studies. Studies in animals have also suggested their beneficial effects in attenuating neuropathic pain in various animal models of neuropathy. In these studies, their usefulness has been ascribed to cholesterol-independent actions, including anti-inflammatory, antioxidant, and neuromodulatory effects. On the contrary, clinical evidence suggests that statin administration in patients is associated with development of neuropathy, suggesting the dichotomous role of statins in neuropathic pain. The present review discusses the pain-attenuating as well as pain-inducing role of statins in preclinical and clinical studies, respectively. Furthermore, the review provides mechanistic insight to explain the paradoxical nature of this class of drugs in neuropathy in preclinical and clinical studies.PerspectiveThe article reviews the pain-inducing role of statins in clinical studies and its neuropathic pain–attenuating role in preclinical studies with possible mechanisms. Understanding key differences in mechanisms may help to attenuate pain induction in the clinical setting and may possibly project statins as neuropathic pain–attenuating agents.