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Pain Management of Neuropathic Pain – Current Insights and Future Perspectives Howard S Smith, 1 Sukriye Damla Kara 2 and Charles E Argoff 3 1. Professor and Academic Director of Pain Management, Department of Anesthesiology, Albany Medical College; 2. Undergraduate Student, University of Rochester; 3. Professor of Neurology and Director, Comprehensive Pain Center, Department of Neurology, Albany Medical College Abstract The management of neuropathic pain remains very challenging and very much an art. Despite the publication of multiple consensus guidelines on the management of neuropathic pain, a significant subpopulation of patients with neuropathic pain are not afforded adequate relief, employing various treatment algorithms with conventional pharmacological therapeutic strategies. First-line agents for the treatment of neuropathic pain include: tricyclic antidepressants, selective serotonin/norepinephrine re-uptake inhibitors, calcium channel α2-δ ligands and, in certain cases of focal neuropathic pain, a lidocaine patch. Novel analgesics under development may include: purinergic receptor modulators, cannabinoid receptor modulators, neurokinin-1 (NK-1) receptor modulators, glial modulators, rostral ventral medulla ‘on-cell’ modulators, chemokine receptor modulators, toll-like receptor modulators, modulators of tetrahydrobiopterin synthesis and/or chemically re-engineered conotoxins. It is hoped that future agents and/or combinations of agents may be helpful to this refractory subpopulation. Keywords Neuropathic, pain, treatment, calcium channel α2-δ ligand, antidepressants Disclosure: Howard S Smith and Sukriye Damla Kara have no conflicts of interest to declare. Charles E Argoff has received an honorarium and/or grant from Endo, Pfizer, Lilly, Forest and Neurogesx for his role as advisor, investigator and member of their speaker bureau. He has also received an honorarium from King, Sanofi-Aventis, Boehringer Ingelheim, Nuvo Research and Jazz for his role as advisor and from Picara for participation on their speaker bureau. Received: 1 February 2012 Accepted: 19 March 2012 Citation: European Neurological Review, 2012;7(1):72–5 Correspondence: Howard S Smith, Professor and Academic Director of Pain Management, Department of Anesthesiology, Albany Medical College, 47 New Scotland Avenue, MC-131, Albany, NY 12208, US. E: smithh@mail.amc.edu Neuropathic Pain Definition, Diagnosis and Clinical Presentation Neuropathic pain (NP) originates as a result of a lesion or disease (e.g., diabetes, herpes zoster, HIV infection, chemotherapy or surgery) pertaining to the somatosensory system. 1 NP can be classified as peripheral or central depending on where the lesion/disease is located. 2 The clinical presentation of NP includes both positive and negative sensory phenomena: e.g., pain and lack of sensation. The presence of NP can be categorised in three groups depending on the certainty of its existence: the ‘definite’ and ‘probable’ levels indicate that the presence of NP is established, and the ‘possible’ level does not confirm the existence of this condition. 2 These levels are assigned by using the NP grading system, which consists of four criteria: • pain with a distinct neuroanatomically plausible distribution; • a history suggestive of a relevant lesion or disease affecting the peripheral or central somatosensory system; • demonstration of the distinct neuroanatomically plausible distribution by at least one confirmatory test; and • demonstration of the relevant lesion or disease by at least one confirmatory test. If all of the four criteria stated above are met, the diagnosis of definite NP is made. Probable NP is present if the first, second and either the third or fourth criteria are met. The diagnosis of possible NP requires the first two criteria without the third or fourth. If the patient fails to exhibit the criteria for these three levels, the NP is considered as absent. 2 Commonly used recent screening tools to identify NP include 72 Leeds assessment of neuropathic symptoms and signs, Douleur neuropathique 4 questions, Neuropathic questionnaire, painDETECT and ID Pain. Bennett et al. conducted research in 2007 investigating these five screening tools and noted that three symptomatic items (‘prickling, tingling, pins and needles’, ‘electric shocks or shooting’ and ‘hot or burning’) were found in all tools. Also ‘numbness’ and ‘pain evoked by light touching’ were present in 80 % of the tools investigated in Bennett et al.’s research. 3 Quantitative sensory testing (QST) is one of the tools useful in evaluating sensation, focusing on the definition of the stimulus properties, the quantity of sensory intensity and the quality of sensation. QST, skin biopsies, imaging electrodiagnostic studies, pertinent ancillary data and the symptoms exhibited by the patient should be studied while treating the NP. The clinician should consider a ‘rational polypharmacotherapy’ for the case if a single agent is not enough to relieve the NP. 4 The illness or injury preceding NP may present itself with both medical and psychiatric co-morbidities, disturbing the diagnosis and assessment of NP. Backonja and Argoff 5 suggested an outline of multidimensional pain assessment (MDPA) to establish the complete clinical diagnosis of individual patients. Multiple dimensions of NP include medical aetiology, pain management, psychiatric co-morbidities and quality of life/ability to function. Ranking each dimension as ‘none’, ‘mild’, ‘moderate’ or ‘severe’ helps assess multidimensional pain. Treatment of Neuropathic Pain The treatment of NP is difficult because less than half of patients receive satisfactory pain relief (>30 % reduction) while side effects are common. Although being treated with multiple medications, studies have shown that NP patients continue to have pain of moderate severity. 6 O’Connor © TOUCH BRIEFINGS 2012