Neuropathic pain is a complex and often disabling condition and many people suffer moderate or severe pain for many years, affecting quality of life. This condition is difficult to treat and typically only 40% to 60% of people with this condition achieve partial relief.
Neuropathic pain is pain coming from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (for example, a fall or cut, or arthritic knee). Neuropathic pain is often treated by different medicines to those used for pain from damaged tissue. Medicines that are sometimes used to treat neuropathic pain can have damaging side effects and therefore people are now trying herbal products to help relieve pain instead.
We conducted a search for relevant clinical trials in March 2018. We looked for studies in adults suffering from moderate neuropathic pain who took some form of herbal product, either by consuming it in their diet, in tablet form, or by applying it to the skin to relieve pain. We also collected information on side effects these herbal products might have.
We included two studies with 128 participants. Study size ranged from 54 to 74 participants with an age range of 21 to 85 years. Both studies included men and women. Both studies compared herbal medicines (nutmeg or St John’s wort) to placebo and allowed continued use of painkillers. Both studies reported side effects.
There were no reports from participants of any reduction in pain intensity of 30% or above and there was no observable reduction in the total pain score in response to either nutmeg or St John’s wort. There were also no reductions in dropout rates or number of side effects between the treatment and placebo.
Quality of the evidence
We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident.
Only two small studies met this review’s search criteria. Neither provided any high-quality evidence for either possible benefits or harms. We judged the evidence to be of very low quality. Thus, results from the studies contained in this review are very uncertain and prevent any meaningful conclusions. Larger, high-quality studies are needed to assess accurately if herbal products are of any benefit or have the potential to harm when used to treat adults with neuropathic pain.
There was insufficient evidence to determine whether nutmeg or St John's wort has any meaningful efficacy in neuropathic pain conditions.
The quality of the current evidence raises serious uncertainties about the estimates of effect observed, therefore, we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Neuropathic pain is a consequence of damage to the central nervous system (CNS), for example, cerebrovascular accident, multiple sclerosis or spinal cord injury, or peripheral nervous system (PNS), for example, painful diabetic neuropathy (PDN), postherpetic neuralgia (PHN), or surgery. Evidence suggests that people suffering from neuropathic pain are likely to seek alternative modes of pain relief such as herbal medicinal products due to adverse events brought about by current pharmacological agents used to treat neuropathic pain. This review includes studies in which participants were treated with herbal medicinal products (topically or ingested) who had experienced neuropathic pain for at least three months.
To assess the analgesic efficacy and effectiveness of herbal medicinal products or preparations for neuropathic pain, and the adverse events associated with their use.
We searched CENTRAL and the Cochrane Database of Systematic Reviews, MEDLINE, Embase, CINAHL and AMED to March 2018. We identified additional studies from the reference lists of the retrieved papers. We also searched trials registries for ongoing trials and we contacted experts in the field for relevant data in terms of published, unpublished or ongoing studies.
We included randomised controlled trials (including cross-over designs) of double-blind design, assessing efficacy of herbal treatments for neuropathic pain compared to placebo, no intervention or any other active comparator. Participants were 18 years and above and had been suffering from one or more neuropathic pain conditions, for three months or more.
We applied no restrictions to language or gender. We excluded studies monitoring effects of isolated, single chemicals derived from the plant or synthetic chemicals based on constituents of the plant, if they were not administered at a concentration naturally present within the plant.
We excluded studies monitoring the effects of traditional Asian medicine and Cannabinoids as well as studies looking at headache or migraine as these treatments and conditions are addressed in distinct reviews.
We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion, assessed risk of bias, and extracted data. We calculated the risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNTB). The primary outcomes were participant-reported pain relief of 30%, or 50%, or greater, and participant-reported global impression of clinical change (PGIC). We also collected information on adverse events. We assessed evidence using GRADE and created a 'Summary of findings' table.
We included two studies (128 participants). Both diabetic neuropathy and non-diabetic neuropathic pain conditions were investigated across these two studies.
Two herbal medicinal products, namely nutmeg (applied topically as a 125 mL spray for four weeks, containing mace oil 2%, nutmeg oil 14%, methyl salicylate 6%, menthol 6%, coconut oil and alcohol) and St John's wort (taken in capsule form containing 900 μg total hypericin each, taken three times daily, giving a total concentration of 2700 mg for five weeks). Both studies allowed the use of concurrent analgesia.
Both reported at least one pain-related outcome but we could not carry out meta-analysis of effectiveness due to heterogeneity between the primary outcomes and could not draw any conclusions of effect. Other outcomes included PGIC, adverse events and withdrawals. There were no data for participant-reported pain relief of 50% or greater or PGIC (moderate and substantial) outcomes.
When looking at participant-reported pain relief of 30% or greater over baseline, we observed no evidence of a difference (P = 0.64) in response to nutmeg versus placebo (RR 1.12, 95% confidence interval (CI) 0.69 to 1.85; 48.6% vs 43.2%). We downgraded the evidence for this outcome to very low quality.
We observed no change between placebo and nutmeg treatment when looking at secondary pain outcomes. Visual analogue scale (VAS) scores for pain reduction (0 to 100, where 0 = no pain reduction), were 44 for both nutmeg and placebo with standard deviations of 21.5 and 26.5 respectively. There was no evidence of a difference (P = 0.09 to 0.33) in total pain score in response to St John’s wort compared to placebo, as there was only a reduction of 1 point when looking at median differences in change from baseline on a 0 to 10-point numeric rating scale.
There was a total of five withdrawals out of 91 participants (5%) in the treatment groups compared to six of 91 (6.5%) in the placebo groups, whilst adverse events were the same for both the treatment and placebo groups.
We judged neither study as having a low risk of bias. We attributed risk of bias to small study size and incomplete outcome data leading to attrition bias. We downgraded the evidence to very low quality for all primary and secondary outcomes reported in this review. We downgraded the quality of the evidence twice due to very serious limitations in study quality (due to small study size and attrition bias) and downgraded a further level due to indirectness as the included studies only measured outcomes at short-term time points. The results from this review should be treated with scepticism as we have very little confidence in the effect estimate.