Neuropathic Pain 2
By Prof. Tissa Wijeratne and Prof. Robert D Helme
Neuropathic pain is challenging to manage, and many patients have pain that is refractory to currently available treatments for NP. In randomized trials (RCTs) that have studied drug therapy, between 2 and 8 patients need to be treated for one to achieve a 50% reduction in pain.
Dworkin and colleagues published a stepwise pharmacological approach in treatment of neuropathic pain.
The first step is to establish a correct diagnosis of NP. Establishing the cause of the NP may lead to effective treatment of the cause, and identify related comorbidities.
The second step is to initiate treatment of the NP with one or more of the following.
· Tricyclic antidepressant (eg. amitriptyline, nortriptyline) or an SNRI (eg duloxetine, venlafaxine)
· Anti-epileptic drugs (eg. Gabapentin, pregabalin)
· Local anaesthetics (eg. topical and parenteral lidocaine )
Strong, (eg. opioids) or weak analgesics (eg. tramadol) alone or in combination with one the above; it should be noted that effective combination trials are rarely reported)
The third step is to reassess the patients’ pain and quality of life. Continue the current treatment if there is a adequate analgesia (average pain reduced to 3/10 severity this is not a common measure of efficacy) with no major side effects. If average pain relief remains higher than 4/10 severity after an adequate trial add one of the other front line medication from the above. If there is no adequate pain relief after an adequate trial (average pain does not reduce to 3/10 severity) switch to an alternative frontline medication.
Step four is to consider second or third line medication after trials with first line medications or a referral to a pain specialist/pain management centre.
The European Federation of Neurological Societies (EFNS) have produced guidelines on pharmacological treatment of NP. These guidelines were revised and republished in 2010. The EFNS guidelines classify the evidence of pharmacological treatment for commonly studied neuropathic pain conditions as follows:
Diabetic neuropathic pain
Gabapentin, Pregabalin, TCA and Duloxetine recommended as first line treatment. Opioids and Tramadol recommended as second line treatment.
Carbamazepine and oxcarbazepine regarded as first line treatment. Surgery is the second line treatment. (Common practice now is to use a gabapentanoid after tegretol as they are quite useful)
Post Herpetic Neuralgia
Gabapentin, Pregabalin, TCA and Lidocaine (topical) regarded as first line treatment. Topical capsaicin and Opioids regarded as second line treatment.
Gabapentin, Pregabalin and TCA regarded as first line treatment. Cannabinoids (MS), Lamotrigine, Opiods and Tramadol regarded as second line treatment. (We believe the evidence for gabapentanoids is weak; TCA has strong evidence)
It is intriguing to note that only a proportion of patients with lesions in the somatosensory system develop neuropathic pain. Age, gender, emotional and cognitive features, pain intensity before and after the lesion may act as risk factors and also demonstrate that there are other factors in addition to nerve lesions that contribute to the neuropathic pain. For example, recent research in animal models points to the involvement of cytokines in the CNS in the pathogenesis of neuropathic pain with exciting possibilities for new effective treatments in selected cases. It is therefore becoming increasingly important to look at the mechanism of pain in each and every individual patient with a view to targeting individual patient specific, multi-disciplinary approaches to management of pain in order to alleviate the suffering of patients with neuropathic pain.
Aminoff JM, Boller F, Swaab FD. Pain: Handbook of Clinical neurology: Elsevier; 2006.
Amir R, Kocsis JD, Devor M. Multiple interacting sites of ectopicspike electrogenesis in primary sensory neurons. J Neurosci 2005; 25: 2576–85.
Attal N, Cruccu G, Baron R et al. EFNS guidelines on the pharmacological treatment of neuropathic pain:2010 revision. Eur J Neurol 2010; 17: 1113-1123.
Bahia PK, Suzuki R, Benton DC et al. A functional role for small conductance calcium-activated potassium channels in sensory pathways including nociceptive processes. J Neurosci 2005;25: 3489–98.
Baron R. Mechanisms of disease: neuropathic pain—a clinical perspective. Nat Clin Pract Neurol 2006; 2: 95–106.
Bennet MI et al. Using screening tools to identify neuropathic pain. Pain 2007;127:199-203.
Caterina MJ, Julius D. The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 2001; 24: 487–517.
Cruccu G, Aminoff MJ, Curio G, Guerit JM, Kakigi R, et al. (2008) Recommendations for the clinical use of somatosensory-evoked potentials. Clin Neurophysiol.2008; 119: 1705–1719.
Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpa¨a¨ M et al. (2004) EFNS guidelines on neuropathic pain assessment. Eur J Neurol.2004;11:153–162.
Cruccu G, Truini A. (2009) Tools for Assessing Neuropathic Pain. PLoS Med 6(4): e1000045.doi:10.1371/journal.pmed. 1000045.
Dworkin RH, O’Connor AB et al. Recommendation for the Pharmacological Management of Neuropathic Pain: An overview and Literature Update. Mayo Clin Proc.2010;85(3)(suppli):S3-S14.
Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007; 132 (3):237-251.
England JD, Gronseth GS, Franklin G,Carter GT, Kinsella LJ et al. Evaluation of distal symmetric polyneuropathy: The role ofautonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Muscle Nerve 2009;39: 106–115.
Finnerup NB, Jensen TS. Mechanism-based classification of neuropathic pain: A critical analysis. Nature Clinical Practice Neurology 2006; 2: 107-115.
Freynhagen R, To¨ lle TR, Baron R. Pain DETECT – ein Palmtopbasiertes Verfahren fu¨ r Versorgungsforschung, Qualita¨tsmanagement und Screening bei chronischen Schmerzen. Akt. Neurol 2005; 34: 641.
Garcia-Larrea L, Convers P, Magnin M, Andre´- Obadia N, Peyron R et al. (2002) Laser-evoked potential abnormalities in central pain patients: The influence of spontaneous and provoked pain. Brain .2002; 125: 2766–2781.
Granovsky Y, Matre D, Sokolik A, Lorenz J, Casey KL. Thermoreceptive innervation of human glabrous and hairy skin: A contact heat evoked potential analysis. Pain .2005; 115: 238–247.
Hains BC, Waxman SG. Sodium channel expression and the molecular pathophysiology of pain after SCI. Prog Brain Res 2007; 161: 195–203.
Hansson P. Neuropathic pain: clinical characteristics and diagnostic workup. Eur J Pain .2002;6 (suppl A):47–50.
Jensen TS, Sindrup SR, Bach FW. Test the classification of pain: reply to Mitchell Max. Pain .2002; 96:407–408.
Krause SJ, Backonja MM. Development of a Neuropathic Pain Questionnaire. Clin J Pain 2003; 19: 306–14.
Lai J, Hunter JC, Porreca F. The role of voltage-gated sodium channels in neuropathic pain. Curr Opin Neurobiol 2003; 13: 291–97.
Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI et al. (2005) EFNS guidelines on the use of skin biopsy in thediagnosis of peripheral neuropathy. Eur J Neurol .2005; 12: 747–758.
Ma W, Zhang Y, Bantel C, Eisenach JC. Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2C-adrenoceptor co-expression and functional inhibition by clonidine. Pain 2005; 113: 386–94.
Nystrom B, Hagbarth KE. Microelectrode recordings from transected nerves in amputees with phantom limb pain. Neurosci Lett 1981; 27: 211–16.
Orstavik K, Jorum E. Microneurographic findings of relevance to pain in patients with erythromelalgia and patients with diabetic neuropathy. Neurosci Lett 2010; 470: 108–04.
Orstavik K, Namer B, Schmidt R, Schmelz M, Hilliges M,Weidner C. Abnormal function of C-fi bers in patients with diabetic neuropathy. J Neurosci 2006; 26: 11287–94.
Orstavik K, Weidner C, Schmidt R et al. Pathological C-fibres in patients with a chronic painful condition. Brain 2003; 126: 567–78.
Portenoy R. for the ID Pain Steering Committee. Development and testing of a neuropathic pain screening questionnaire: ID Pain. Curr Med Res Opin 2006;22: 1555–65.
Ralf Baron, Andreas Binder, Gunnar Wasner. Neuropathic pain: diagnosis, pathophysiological mechanisms and treatment. Lancet Neurol 2010; 9: 807–19.
Treede RD, Lorenz J, Baumga¨ rtner U (2003) Clinical usefulness of laser-evoked potentials. Neurophysiol Clin .2003; 33: 303–314.
Treede et al. Neuropathic Pain. Redefinition and a grading system for clinical and research purposes. Neurology .2008; 70: 1630-1635.
Truini A, Galeotti F, Haanpaa M, Zucchi R, Albanesi A et al. Pathophysiology of pain in postherpetic neuralgia: A clinical and neurophysiological study. Pain .2008;140: 405–410.
Wu G, Ringkamp M, Murinson BB et al. Degeneration of myelinated eff erent fi bers induces spontaneous activity in uninjured C-fi ber eff erents. J Neurosci 2002; 22: 7746–53.
Yawn BP. et al. The prevalence of neuropathic pain: Clinical evaluation compared with screening tools in a community population. Pain Med.2009;10(3):586-593.
Sri Lanka Association for the Study of Pain
The Sri Lankan Chapter of the International Association for the Study of Pain
© January 2014. Sri Lanka Association for the Study of Pain (SLASP). All Rights Reserved.
For Comments firstname.lastname@example.org