Neuropathic Pain Medication

Original Editor - Lucinda hampton Top Contributors - Lucinda hampton

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Introduction

Neuropathic pain is relatively common and often poorly treated. Neuropathic pain is characterised by abnormal hypersensitivity to stimuli (hyperalgesia) and nociceptive responses to non-noxious stimuli (allodynia). Neuropathic pain can be a consequense of metabolic disorders, viral infections, and autoimmune diseases affecting the central nervous system (CNS)[1]. Neuropathic pain in the general population is estimated to have a prevalence ranging between 3% and 17%.

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Currently existing therapies for neuropathic pain are far from effective. All current treatments are symptomatic rather than disease-modifying or curative. Only 40%–50% of patients reach the magic number of 30% pain relief in the clinical setting and 50%–60% of patients get no pain relief.[2] Often a combination of drugs are taken.

The management of neuropathic pain is challenging and, as with all pain, should be approached with a biopsychosocial framework. There are several options for drug treatment as part of an overall approach to improve patients’ quality of life and function.

Additionally a range of therapeutic modalities is emerging, targeting a variety of mechanisms, that may in the future have better client outcomes. eg. Nanotechnologies have enabled novel solutions for the treatment of various diseases. Nanodrug delivery systems present some advantages than conventional drug delivery systems such as high cellular uptake and reduced side effects[3]

Current Medication Recommendations

The below video gives a 12 minute overview of the state of play regarding Neuropathic pain medications

[4]

Guidelines from different countries offer consistent recommendations for treating neuropathic pain. Effective first and second-line therapies include tricyclic antidepressants, duloxetine, venlafaxine, gabapentin, pregabalin and topical lidocaine[5].

The Special Interest Group on Neuropathic Pain 2019 recommended this approach for medication treating neuropathic pain[1].

First-line therapy:

  • Anti Epileptic drugs (AED's). 1.Gabapentinoids, Gabapentin 150–600 mg/day. AE (adverse effects) Lethargy, vertigo, peripheral swelling, blurred vision; 2.Pregabalin 300–3600 mg/day AE Lethargy, vertigo, peripheral swelling, increased body weight
  • Tricyclic antidepressants (TCAs): Amitriptyline 10–150 mg/day AE Anticholinergic effects, QT prolongation (arrhythmia), suicide risk, urinary retention
  • Serotonin–norepinephrine reuptake inhibitors (SNRI): Duloxetine 20–120 mg/day AE Nausea, lethargy, constipation, ataxia, dry mouth; Venlafaxine 150–225 mg/day AENausea, vertigo, lethargy, hyperhidrosis, hypertension

Second-line therapy;

  • Opioids: Tramadol 25–400 mg/day AE Nausea/vomiting, constipation, lethargy, seizures, ataxia; Tapentadol 50–600 mg/day AE Nausea/vomiting, constipation, lethargy, seizures, ataxia
  • Topical treatment Lidocaine 5% patches or gel AE Local erythema, itching and rash
  • Capsaicin 8% patches AE Pain, erythema, itching; rare cases of high blood pressure

Third-line therapy

  • Strong opioids; Morphine 10–120 mg/day AE Nausea, vomiting, constipation, dizziness and lethargy; Oxycodone 10–120 mg/day AE Nausea/vomiting, constipation, lethargy, respiratory control
  • Neurotoxin Botulinum toxin 25–300 U BTX-A 0.9% saline AE Pain at injection site

As a Physiotherapist it is important to be aware of which medications can impact on our patients safety, medication is obviously not within a physiotherapist job role specifically however knowing what the potential impact of some medications can be very valuable. See Medication and Falls, Medication and Older People to understand the risks associated with these medications, falls risk being a very important issue to be aware of.

Medications

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Anti Epileptic Drugs (AEDs): AEDs are used extensively worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. [6]The pathophysiological processes involved in neuropathy lead to is neuronal hyperexcitability. The main action of the AEDs is to decrease hyper excitability.

Antidepressants: Several antidepressants have been efficacious in the management of chronic neuropathic pain, including the tricyclic antidepressants. Tricyclic antidepressants may relieve neuropathic pain by their unique ability to inhibit presynaptic reuptake of the biogenic amines serotonin and noradrenaline, but other mechanisms such as N-methyl-D-aspartate receptor and ion channel blockade probably also play a role in their pain-relieving effect.[7]The selective serotonin reuptake inhibitors have either been less robust (paroxetine, citalopram) or lacked any efficacy at all (fluoxetine)[8]

Opiods: Often discouraged because of concerns about overdoses, abuse, dependence, and the effects of long-term use. High doses of opioids typically are needed to provide significant pain relief for neuropathic conditions[9]

Topical Treatments: Usually available as a patch, gel, or cream, topical treatments can be helpful for localized neuropathic pain. The medication is absorbed into the skin, either numbing the area or relieving pain. An option for individuals who cannot tolerate oral medication. Little of the medication reaches the bloodstream, so cognitive side effects are avoided. Multiple applications are typically needed for significant pain relief.[9]

Emerging Medications and Modes of delivery

Most of the available treatments for neuropathic pain have moderate efficacy and present side effects that limit their use. As such the need exists to identify new effective therapeutic strategies in neuropathic pain management. Some of the new approaches are listed below[1]

  • Cannabis.jpg
    Several clinical trials have shown the potential effectiveness of cannabis-derived compounds in the treatment of pain associated with diabetes, chemotherapy, and multiple sclerosis.
  • Sativex already approved by the FDA for the treatment of spasticity in multiple sclerosis patients is considered as an alternative for patients suffering from neuropathic pain.
  • Nanotechnology-based drug delivery systems are promising tools to resolve the low solubility and the bioavailability of some compounds. The use of nano carriers could be an area of growth and clinical benefit.
  • Repurposing drugs currently approved for other indications that have already shown efficacy in animal models of neuropathic pain.

Conclusion

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Neuropathic pain in the general population is estimated to have a prevalence ranging between 3% and 17%. Neuropathic pain management focuses on treating symptoms, and only in some pathological condition, the etiological causes can be treated relieving pain[6]. A range of therapeutic modalities is emerging, targeting a variety of mechanisms. In the near future we may be able to treat neuropathic pain in a more precise manner.

References

  1. 1.0 1.1 1.2 Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431761/
  2. Backonja M, Woolf CJ. Future directions in neuropathic pain therapy: closing the translational loop. The oncologist. 2010 May 1;15(Supplement 2):24-9. Available from: https://theoncologist.alphamedpress.org/content/15/suppl_2/24.full (last accessed 26.9.2019)
  3. Nanowerk Nanotechnology based drug delivery systems for nanomedicine September 2018. Available from: https://www.nanowerk.com/spotlight/spotid=51090.php (last accessed 26.9.2019)
  4. J Kattner What is the best medication for nerve pain Available from: https://www.youtube.com/watch?v=Qj-dQ5rC7rs&app=desktop (last accessed 26.9.2019)
  5. Krista G Brooks Tiffany L Kessler. Treatments for neuropathic pain. 1.12.2017 Available from: https://www.pharmaceutical-journal.com//research/review-article/treatments-for-neuropathic-pain/20203641.fullarticle?firstPass=false (last accessed 26.9.2019)
  6. 6.0 6.1 Sidhu HS, Sadhotra A. Current status of the new antiepileptic drugs in chronic pain. Frontiers in pharmacology. 2016 Aug 25;7:276. Available from: https://www.frontiersin.org/articles/10.3389/fphar.2016.00276/full (last accessed 27.9.2019)
  7. Sindrup SH, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology. 2005 Jun;96(6):399-409. Available from: https://www.ncbi.nlm.nih.gov/m/pubmed/15910402/ (last accessed 27.9.2019)
  8. Sansone RA, Sansone LA. Pain, pain, go away: antidepressants and pain management. Psychiatry (Edgmont). 2008 Dec 5;5(12):16. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729622/ (last accessed 27.9.2019)
  9. 9.0 9.1 Spine Health 1.9.2017 Medications for Neuropathic Pain Available from: https://www.spine-health.com/treatment/pain-management/medications-neuropathic-pain (last accessed 27.9.2019)