Efficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis

Abstract

Objective To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. Methods A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of Bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. Results Nine studies (n = 863) were included (5 randomized controlled trials [RCTs], 2 open-label non-comparative studies and 2 comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of 3 RCTs, N-acetylcysteine did not reduce pain intensities (SMD -0.21, 95% CI -0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI -0.33 to 0.75) or quality of life (SMD 0.60, 95% CI -4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. Conclusions While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine’s role, if any, in pain medicine.

The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders

“…Chronic pain is heterogeneous; however, some chronic pain states are associated with increased oxidative stress [ 198 ]. All types of chronic pain involve the development of nociceptive sensitization [ 14 ].…”

Men suffering from category III chronic prostatitis may benefit from N‐acetylcysteine as an adjunct to alpha‐blockers

“…This potential mechanism may ameliorate the urinary symptoms resulting from periurethral fibrosis 35‐37 . Beyond this, recent research has revealed that NAC may also have antinociceptive and analgesic effects; surprisingly enough, favorable effects of NAC supplementation in various types of chronic pain syndromes have been demonstrated in a number of clinical studies 23 . Although the precise mechanism by which NAC exerts its antinociceptive and analgesic effect is not known; it is suggested that it also may be related to its anti‐inflammatory and antioxidant actions 19,38‐41 .…”

“…[35][36][37] Beyond this, recent research has revealed that NAC may also have antinociceptive and analgesic effects; surprisingly enough, favorable effects of NAC supplementation in various types of chronic pain syndromes have been demonstrated in a number of clinical studies. 23 Although the precise mechanism by which NAC exerts its antinociceptive and analgesic effect is not known; it is suggested that it also may be related to its anti-inflammatory and antioxidant actions. 19,[38][39][40][41] Thus, NAC, through its antinociceptive and analgesic activities, may also be able to relieve the pain symptoms associated with CP/CPPS.…”

“…A total of 63 patients who fulfilled the inclusion and exclusion criteria were randomly allocated in a 1:1 ratio to take NAC+tamsulosin (32 cases) or placebo+tamsulosin (31 cases). We chose a dose of 1,200 mg of NAC per day in our study based on the previous research that oral NAC at doses of 600‐2400 mg daily could alleviate symptoms of chronic pain syndromes 23 . we chose a dose of 1200 mg of NAC per day in our study.…”

“…We chose a dose of 1,200 mg of NAC per day in our study based on the previous research that oral NAC at doses of 600-2400 mg daily could alleviate symptoms of chronic pain syndromes. 23 we chose a dose of 1200 mg of NAC per day in our study. All patients took tamsulosin capsules at a dose of 0.4 mg once daily at bedtime.…”