Impact of Adjuvant Analgesics on Outcomes of Spinal Cord and Peripheral Nerve Stimulation: A Scoping Review.

Introduction: Spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are used to treat refractory pain, but even well-selected patients can fail to have analgesic benefit following implantation. The analgesia afforded by SCS/PNS may be enhanced or attenuated by the ongoing use of analgesic medications that are often consumed by patients who receive SCS and PNS implants. We undertook a scoping review to scan and summarize the evidence for impact of adjuvant pharmacotherapy on SCS and PNS therapy in animal and human settings.

Materials And Methods: A comprehensive medical literature review was performed on major medical databases including MEDLINE, EMBASE, CINAHL, CENTRAL and Google Scholar from inception until July 31, 2024, for both human and animal studies. Data on the effect of pharmacotherapy on SCS analgesic efficacy and adverse effects was extracted and summarized using the Arksey and O'Malley population, concept, context (PCC) model for scoping reviews.

Results: Twenty-seven studies, nine on animals and 18 on humans were identified. In human studies, SCS non-responders with neuropathic pain had analgesia restored by addition of intrathecal baclofen and clonidine. Patients who eliminated opioid use, or who were opioid naive, had superior clinical outcomes with SCS compared to those continuing opioids. Cannabinoids were associated with enhanced SCS analgesia. Patients on benzodiazepines had higher likelihood of SCS explantation. Animal studies showed intrathecal ketamine restored SCS analgesic benefits, while baclofen, clonidine, cannabinoid receptor agonists, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, augmented SCS responses while benzodiazepines were found to inhibit analgesic effects of PNS (see Figure 1-Graphical abstract).

Conclusions: This review indicates that adjunctive analgesic therapy may play a significant role in either enhancing or attenuating analgesic benefits from SCS and PNS. By optimizing the use of analgesic medications, it may be possible to restore or enhance pain relief from both SCS and PNS.