Little Evidence Conclusively Supports Use of N-Acetylcysteine for Chronic Pain

Few studies support the use of N-acetylcysteine (NAC) in chronic pain management, despite some evidence suggesting NAC may offer an analgesic effect for some pain conditions, according to findings from a meta-analysis published in Pain Medicine.

Canadian researchers conducted a systematic review of studies that discussed the use of NAC in the management of chronic pain in adults. A pooled meta-analysis was performed for 9 studies that included 863 patients with any persistent or recurrent chronic pain condition lasting longer than 3 months.

Improvement in patient-reported pain intensities was the primary outcome. Additional outcomes included adverse events (AEs), sleep effects, and quality of life (QoL).

The 5 randomized-controlled trials, 2 open-label noncomparative studies, and 2 comparative studies included patients with either sickle cell disease, complex regional pain syndrome, pelvic pain/endometriosis, rheumatoid arthritis, diabetic neuropathy, or chronic neuropathic pain.

In the meta-analysis of 3 randomized controlled trials, the use of NAC was not associated with reduced pain intensities as assessed via visual analog scales or numeric rating scales (standardized mean difference [SMD], -0.21; 95% CI, -0.33 to 0.75). Additionally, treatment with NAC did not improve QoL (SMD, 0.60; 95% CI, -4.44 to 5.64; P =.06) but was associated with a small significant effect on functional outcomes according to a post hoc sensitivity analysis (SMD, 0.32; 95% CI, 0.07-0.57; P =.02). In one study, NAC and pregabalin had a significantly different effect on participants’ sleep (-5.60) compared with participants in the control group (-3.91; P <.001).

The reporting of AEs was inconsistent across studies, and only 6 studies reported the nature of AEs experienced by patients. Given the inconsistent nature of the AE reporting, the investigators wrote that they could not make a conclusion on the safety of NAC for the management of chronic pain.

A limitation of this analysis was the inclusion of studies that featured “substantial differences” in regard to patients’ pain disorders, NAC doses, duration of treatments, and follow-up times.

The investigators added that it may be important to study “the role of NAC in chronic pain conditions that” were not evaluated in this meta-analysis, including “where antioxidants may play a beneficial role, such as fibromyalgia, multiple sclerosis, osteoarthritis, and chronic neuropathic pain.”


Mohiuddin M, Pivetta B, Gilron I, Khan JS. Efficacy and safety of N-acetylcysteine for the management of chronic pain in adults: a systematic review & meta-analysis. Pain Med. Published online February 9, 2021. doi:10.1093/pm/pnab042