Neuropathic pain is common in patients with multiple sclerosis

Almost all patients with multiple sclerosis (MS) experience pain, whether acute or chronic, throughout the course of their disease [1, 2]. Neuropathic pain (which can present in up to a third of patients with MS [1]) can usually be classified as either central (due to a lesion or a central somatosensory nervous system condition) or peripheral (due to metabolic, infectious, genetic, autoimmune, neurotoxic, traumatic or other causes) [2]. There is an unmet need in terms of the effective management of pain in these patients, whether from inaccurate/late diagnosis, ineffective treatment(s) or other medical/personal/societal factors [2]. Evidence for the drugs used in treating neuropathic pain in patients with MS are mostly derived from studies in other diseases, therefore newer options are needed, ones with improved efficacy and/or reduced adverse effects [1].

Antidepressants are currently used as first line in the management of neuropathic pain in patients with MS [1, 2]; the combination of duloxetine (a serotonin and norepinephrine reuptake inhibitor) and amitriptyline (a tricyclic antidepressant) confers the greatest efficacy (Table 1) [3]. Note that the dosage for tricyclic antidepressants are lower when used for analgesia [2]. Gabapentin and pregabalin can also be prescribed as first-line options, as recommended by the National Institute for Health and Care Excellence (NICE) [4]. If one of these options is ineffective, one of the other choices can be trialled [4].

Table 1 Brief summary of evidence for pharmacological treatment options for neuropathic pain in patients with multiple sclerosis, as reviewed by Shkodina et al. [1] and Gurba et al. [2]
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This article briefly summarises some pharmacological and non-pharmacological treatment options for the management of neuropathic pain in patients with MS, as reviewed by Shkodina et al. [1] and Gurba et al. [2], and supported by guidance from NICE [3, 4].

Although various options are available, many have limited evidence

Anticonvulsants, which ameliorate the effects of seizures by suppressing the rapid and excessive firing of neurons, are commonly prescribed for neuropathic pain associated with MS [1]. Although a second-line option in neuropathic pain, carbamazepine is recommended as first-line in managing trigeminal neuralgia specifically [4]. While the limited clinical trial data that are available are promising (Table 1), further investigation is required to fully elucidate the use of anticonvulsants in treating neuropathic pain, particularly in patients with MS [1]. Indeed, Cochrane reviews concluded there is no strong evidence for anticonvulsant efficacy in treating neuropathic pain [2].

Opioids are another commonly used form of pain relief in patients with MS; however, the association with mood and anxiety disorders, along with opioid-specific adverse drug effects, precludes it from being a first-line option for many [1]. While tramadol is considered a (short-term) second-line option for neuropathic pain [4], none of the evidence are from patients with MS [2]. Naltrexone has only shown efficacy in MS in a phase II pilot study [5], and morphine has demonstrated only limited efficacy in patients with MS; therefore, further clinical trial data for opioid use in patients with neuropathic pain and MS are needed [1]. Although cannabinoids are an increasingly popular choice for pain management, systematic reviews have concluded that current evidence is not convincing enough for the routine recommendation of cannabinoids as pain relief for neuropathic pain in patients with MS [2].

As MS pain can result from spasticity and muscle spasms, muscle relaxants can be an effective option (Table 1) [1]. NICE guidance recommends oral baclofen as a first-line option for spasticity management in patients with MS, especially if pain relief is a primary goal [3]. Nanomedicine is another emerging field of pharmaceutics that can lead to improved efficacies in neuropathic pain therapies through the modification of a drug’s pharmacodynamic and pharmacokinetic profiles [1]. Nanotechnology has already been implemented for drugs such as doxepin, morphine, baclofen and amitriptyline [1].

Non-pharmacological methods also have a place

In addition to the pharmacological choices summarised above, there are numerous non-pharmacological methods to help manage neuropathic pain in patients with MS (Table 2), albeit with limited evidence of efficacy for many options [3]. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic or direct current stimulation work by applying short, high-intensity magnetic fields or low-amplitude direct currents to the brain (Table 2), changing the excitability of the cerebral cortex and potentially reducing pain [1]. However, the small number of studies (with few patients) and the heterogeneity of the study designs means the evidence is currently limited [1]; further studies are required to confirm the efficacy of non-invasive brain stimulation techniques in reducing pain in patients with MS.

Table 2 Non-pharmacological treatment options for neuropathic pain in patients with multiple sclerosis, as reviewed by Shkodina et al. [1]
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Neurological methods mainly manage trigeminal pain in patients with MS (Table 2). In a meta-analysis, there were no statistically significant differences in efficacy or tolerability between the main neurological methods [11]. Deep brain stimulation, where portions of the brain are stimulated with special impulses via electrodes, is another method that has been used to treat various nervous system diseases; however there is no evidence of efficacy in patients with MS [1].

Psychotherapy is also an important component for treating chronic pain, especially when utilised as part of a multidisciplinary and multimodal management plan (Table 2) [1]. Patients with MS in particular are plagued with depression, anxiety, fatigue and sleep issues, which can exacerbate neuropathic pain and other mental health issues. Physical exercise (including aerobic, balance and stretching exercises such as yoga) may have beneficial effects in patients with MS and chronic pain (Table 2), as it maintains a patient’s general physical condition, reduces coordination issues and generally improves quality of life [1]. However, note that a supervised, combined exercise programme is more useful and effective for a patients with MS than self-directed exercise [3]. Although both psychotherapy and physical exercise are non-pharmacological methods that require further evidence to establish their place in chronic pain management, this does not preclude their clinical use as part of a tailored management plan.

The future of neuropathic pain management is reliant on more data

As is evident from the summaries above, much of the ‘evidence’ for neuropathic pain management in patients with MS is extrapolated data, with very little evidence-based research for healthcare professionals to follow. Therefore, several points must be considered in order to create a more robust management algorithm for MS-induced neuropathic pain [1]:

  • further and fully investigate the efficacy and tolerability of treatment options in the intended population (i.e. patients with MS), including non-pharmacological options

  • longer-term data will be of benefit

  • utilise individualised patient factors to personalise treatment plans

  • education is key for patients

  • encourage multidisciplinary teamwork between healthcare professionals providing pain management care.

Take home messages

  • Neuropathic pain in patients with MS is common and can be debilitating and chronic, and there is a significant need for newer, more effective treatment options

  • Antidepressants are always the first option; tricyclic antidepressants are the most studied, albeit not extensively

  • Although evidence is limited, can consider anticonvulsants, opioids, muscle relaxants and even nanomedicine if first line options fail

  • Non-pharmacological methods are useful adjuncts to manage neuropathic pain in patients with MS, but further investigation is needed