Research

Pharmacotherapeutic options continue to expand for the treatment of chronic non-cancer pain. There has been an increasing emphasis on multimodal analgesia. This strategy employs use of multiple analgesic medications each with a distinct mechanism of action, which when administered concomitantly may provide profound analgesia. The authors describe evidence from randomized controlled trials and systematic reviews on a variety of established medications including anti-inflammatory agents, opioids, anti-convulsants, anti-depressants, N-methyl-D-aspartate receptor antagonists, sodium channel blockers, cannabinoids, and alpha-2-receptor blockers. Furthermore, they provide developing evidence on more novel pharmacotherapeutics including alpha lipoic acid, acetyl-L-carnitine, low dose naltrexone, calcitonin gene-related peptide antagonists, targeted toxin therapy, Nav1.7 inhibitors, neurotensin agonists, purinoceptor antagonists, and sigma-1 receptor antagonists. Furthermore, the authors review the safety and adverse effect profile for these agents. In this era of the opioid epidemic, clinicians should first offer non-opioid analgesics and employ a multimodal analgesic strategy. Current guidelines recommend a personalized approach to the chronic pain treatment, in each case accounting for type, location, severity, and chronicity of pain. Clinicians should also carefully consider the risk-to-benefit ratio to the patient based on the drug side effect profile, patient age, and comorbidities. In accordance with the stepwise approach outlined by the World Health Organization (WHO) analgesic ladder, clinicians should administer non-opioid analgesics plus adjuvant analgesics initially for mild pain, followed by adding weak opioid agonists for moderate pain, and strong opioid agonists and minimally invasive interventions for severe pain.