Complex Regional Pain Syndrome (CRPS/RSD) and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

Abstract

Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS) types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.Bisphosphonates have been used for pathologic conditions associated with abnormal bone metabolism, such as osteoporosis, Paget’s disease and cancer-related bone pain for many years. More recently, results of clinical trials have indicated the potential role of bisphosphonates in the treatment of CRPS/RSD.In this paper we will review the preclinical studies regarding the use of bisphosphonates as analgesics in animal models of neuropathic pain, and also summarize the clinical trials that have been done to date. We will give an overview of bisphosphonate pharmacology and discuss several potential mechanisms by which bisphosphonates may be analgesic in CRPS/RSD and bone pain of noncancer origin.

Emerging targets in treating pain

“…In several small randomized controlled trials, the use of bisphosponates has resulted in improvements in pain and function, suggesting a possible role in neuropathic pain [257,258]. In several small randomized controlled trials, the use of bisphosponates has resulted in improvements in pain and function, suggesting a possible role in neuropathic pain [257,258].…”

Spinal Cord Stimulation as Treatment for Complex Regional Pain Syndrome Should Be Considered Earlier Than Last Resort Therapy

“…There are a variety of medications that have been used to treat the symptoms of CRPS with some success. These range from nonsteroidal anti‐inflammatory drugs (NSAIDs), steroids, and opioid analgesics and medications used to decrease nerve excitability such as anticonvulsants, tricyclic antidepressants, membrane‐stabilizing medications, the N‐methyl‐D‐aspartate (NMDA) receptor antagonist, ketamine , biophosphonates , and thalidomide . Salmon calcitonin for CRPS has been well studied ; however, one randomized controlled trial (RCT) found no more efficacy of the drug when compared with placebo .…”

Komplexes regionales Schmerzsyndrom

“…Der antinozizeptive Effekt der Bisphosphonate scheint aber nicht nur durch eine Hemmung der Osteoklastenaktivität und Osteoklastogenese zurückzuführen zu sein. Es gibt Hinweise, dass die Bisphosphonate auch die Aktivität der Neuropeptide-produzierenden Zellen hemmt (65).…”