REVIEW ARTICLE Pharmacotherapy of Neuropathic Pain Hindol Mondal 1 , Shouvik Choudhury 2 , Abhijit Das 3 , Anup K Bhaacharya 4 A BSTRACT Neuropathic pain (NP), comprising a range of heterogeneous pathophysiological conditions, is often difficult to manage despite a number of treatment guidelines have been published worldwide. Most of the available treatments in these guidelines have moderate efficacy and present side effects that limit their use. Currently, there is a general agreement on appropriate first-line treatment of NP, whereas debate continues regarding second- and third-line treatments. First-line drugs include antidepressants (tricyclic antidepressants (TCAs) and serotonin–noradrenaline reuptake inhibitors (SNRIs)) and gabapentinoids. Second- and third-line drugs for NP include topical lidocaine, topical capsaicin, anticonvulsants, and opioids. A good understanding of pathophysiology of NP with the mechanism of action of currently available drugs along with their side effect profile helps to tailor therapies both to the specific neuropathic disease and to the needs of an individual patient. This review provides an overview of current drugs available for the treatment of NP with an emphasis on their mechanism of action. Keywords: Capsaicin, Gabapentinoid, Neuropathic pain, Serotonin–noradrenaline reuptake inhibitor, Tricyclic antidepressant. Bengal Physician Journal (2019): 10.5005/jp-journals-10070-6114 I NTRODUCTION According to the International Association for the Study of Pain (IASP), neuropathic pain (NP) is described as “pain caused by a lesion or disease of the somatosensory nervous system.” 1 It can be categorized as central or peripheral NP according to its origin. Peripheral NP originates from dysfunction or disease of the peripheral nerve, and conditions responsible for peripheral NP are diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, radicular pain, postsurgical chronic NP, and neuropathic cancer pain. Central NP originates from a central lesion or diseases like stroke, spinal cord injury, and multiple sclerosis. 2 Neuropathic pain is often underdiagnosed and prevalence of NP is difficult to estimate due to the lack of consensus on the definition of NP. In a systematic review of pain with neuropathic characteristics, we have found the incidence between 3% and 17%. 3 Though reports are scant on the prevalence in India, the burden is estimated to be enormous. In a recent evaluation from India, the reported prevalence of diabetic peripheral neuropathy (DPN) was 29.2% in patients with type 2 diabetes mellitus (T2DM). 4 M ANAGEMENT OF N EUROPATHIC P AIN Multiple international guidelines (Table 1) have suggested the following three classes of drugs as first-line agents: TCAs, SNRIs, and gabapentinoids. Rest of the drugs are considered as second- or third-line therapy and used in combination with first-line drugs when they are not effective alone or have low safety profile. 5 Antidepressants Tricyclic antidepressants and SNRIs were found to be effective in reducing NP. Amitriptyline is the most studied TCA and it did not show a dose–response effect. 6 They have been shown to be effective in the treatment of peripheral neuropathy, postherpetic neuralgia, and NP post-spinal cord injury and of limited effect in radiculopathy, HIV, and chemotherapy-induced peripheral neuropathy. 7 The usual starting dose for Indian population is as low as 10 mg, which should be titrated upward slowly to maximum of 50–75 mg in divided doses. Tricyclic antidepressants act predominantly via inhibition of serotonin and noradrenaline reuptake; however, they also block histamine, adrenalin, acetylcholine, and sodium channels, resulting in a wide adverse effect profile. 8 Among the SNRIs, duloxetine and venlafaxine are most commonly studied agents for NP. 6,9 These drugs act by inhibiting noradrenaline and serotonin reuptake in nerve endings and thus increasing their concentration in the descending pain inhibition pathway. 8 Duloxetine is very much effective in diabetic neuropathy and approved by Food and Drug Administration (FDA) for this purpose. Other painful peripheral neuropathy also responds well. 10 In India, the standard dose of duloxetine starts with 20 mg once daily at bedtime, which can be titrated up to 60 mg in divided daily doses. Further higher dose can be given after considering the potential risk arising from different adverse effects and drug interactions. Venlafaxine is initiated at 37.5 mg once at bedtime and can be increased cautiously up to maximum of 225 mg. 11 Gabapentinoids and Other Anticonvulsants Most commonly recommended drugs of this group are pregabalin and gabapentin, which are considered as the first-line therapy. 5,12 They act by blocking the presynaptic α2δ calcium channels in the dorsal horn in the central nervous system and the spinal cord and thus prevent neurotransmitter release. 13 Both the agents are effective in diabetic neuropathy and postherpetic neuralgia. 1–3 Department of Pharmacology, Burdwan Medical College, Bardhaman, West Bengal, India 4 Department of Medicine, Agartala Government Medical College, Agartala, Tripura, India Corresponding Author: Shouvik Choudhury, Department of Pharmacology, Burdwan Medical College, Bardhaman, West Bengal, India, Phone: +91 9083806388, e-mail: [email protected] How to cite this article: Mondal H, Choudhury S, Das A, et al. Pharmacotherapy of Neuropathic Pain. Bengal Physician Journal 2019;6(2):28–30. Source of support: Nil Conflict of interest: None © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons. org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Pharmacotherapy of Neuropathic Pain
May 23, 2023
Neuropathic pain (NP), comprising a range of heterogeneous pathophysiological conditions, is often difficult to manage despite a number of treatment guidelines have been published worldwide. Most of the available treatments in these guidelines have moderate efficacy and present side effects that limit their use. Currently, there is a general agreement on appropriate first-line treatment of NP, whereas debate continues regarding second- and third-line treatments. First-line drugs include antidepressants (tricyclic antidepressants (TCAs) and serotonin–noradrenaline reuptake inhibitors (SNRIs)) and gabapentinoids. Second- and third-line drugs for NP include topical lidocaine, topical capsaicin, anticonvulsants, and opioids.
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