Statins and Neuropathic Pain: A Narrative Review

Abstract

The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes.

Synergistic interaction between B vitamins and statins to counter nociception in rats

“…It is noteworthy that statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans (Bhalla et al, 2014; Pergolizzi Jr. et al, 2020). However, the American Heart Association has stated that “there is no convincing evidence for a causal relationship between statins and peripheral neuropathy” (Newman et al, 2019; Pergolizzi Jr. et al, 2020). In this sense, in US clinical practices, roughly 10% of patients stop taking a statin because of subjective complaints, most commonly muscle symptoms without raised creatine kinase.…”

“…Animal studies that show statins lowering neuropathic pain intensity likely have more to do with anti‐inflammatory effects of statins than the drugs' cholesterol‐lowering effects. In humans, there is some anecdotal evidence that statins have been associated with neuropathic pain, but hard evidence remains elusive (Pergolizzi Jr. et al, 2020).…”

“…(c) downregulating caveolin-1 expression (shown to promote eNOS activity in vitro and in vivo in mice) (Pelat et al, 2003); and…”

Induction of analgesia using atorvastatin in experimental diabetic neuropathy through NMDA receptor and inflammatory cytokines inhibition

“…The excessive level of oxidized low-density lipoproteins leads to the ROS-mediated activation of NF-κB in the endothelial cells of the peripheral nervous system (26). Furthermore, NMDA induces a Ca 2+ -dependent activation of NF-κB, which subsequently results in the activation of inflammatory cascades (27).…”

Statin use and safety concerns: an overview of the past, present, and the future

“…Another case-control study reported a risk of idiopathic polyneuropathy with long-term statin exposure (OR 26.4, CI 7.8-45.4) [53]. A narrative review published in February 2020 has suggested a probable link between statin use and neuropathic pain which could be attributed to impaired mitochondrial transport, vitamin-E deficiency, or decreased pro-inflammatory cytokines but the findings still remain rather inconclusive [54].…”