CAUSE DI DOLORE PERIFERICO E TERAPIE SPECIFICHE

Sul piano farmacologico i modelli più studiati di dolore neuropatico periferico sono le poli- neuropatie dolorose, in particolare quella dia- betica e la nevralgia post-herpetica. (Tabella 4)

Polineuropatie dolorose diabetiche e non diabetiche

Per quanto riguarda le polineuropatie dolo- rose le ultime linee-guida dell’EFNS del 2006 (19) raccomandano come trattamento di prima linea gli antidepressivi triciclici (amitriptilina, clomipramina, desipramina, imipramina), gabapentin (1200-3600 mg/die) e pregabalin (150-600 mg/die). Gli SNRI

venlafaxina e duloxetina sono di seconda scelta per la minor efficacia ma sono farmaci sicuri con meno controindicazioni dei trici- clici. Altri farmaci efficaci nelle polineuropa- tie dolorosa sono gli oppioidi (oxicodone a 37-60 mg/die, tramadolo 200-400 mg/die) e la lamotrigina. Un minimo effetto può aver- si anche con l’uso di capsaicina, mexiletina, oxcarbazepina, SSRI, topiramato. Efficaci Contesto/ malattia distribuzione del dolore farmaci di prima scelta coadiuvanti

Diabete mellito mononeuropatia,

polineuropatia, radicolopatia. Escludere altre cause (la frequenza del dolore neuropatico nel diabete è circa del 16%) antidepressivi triciclici, antiepilettici (gabapentin, pregabalin, lamotrigina), SNRI (duloxetina,venlafaxina), oppioidi In sequenza e, se necessario, in associazione. pomata alla capsaicina

Infezione HIV polineuropatia, mononeuropatia, radicolopatia, mielopatia

Idem in particolare lamotrigina Sclerosi multipla mielopatia, nevralgia

trigeminale, dolori radicolari

Idem e cannabinoidi Infiltrazione

neoplastica e chemioterapia antineoplastica

polineuropatie tossiche amitriptilina, gabapentin ed oppioidi

Alcoolismo polineuropatia, mononeuropatie

idem Herpes zoster radicolare, acuto e cronico

(nevralgia posterpetica) gabapentin, pregabalin, valproato, antidepressivi triciclici, oppioidi pomata alla capsaicina e patch alla lidocaina Nevralgia trigeminale in caso di farmacoresistenza, trattamenti neurolesivi o del conflitto neurovascolare

carbamazepina,

oxcarbazepina, baclofen, lamotrigina)

Amputazione neuroma, arto fantasma triciclici, antiepilettici, morfina, tossina botulinica Lombosciatalgia dermatomerico (la lombalgia

da sola non rientra nel dolore neuropatico)

FANS, paracetamolo, tramadolo,bupropione. Il gabapentin non ha specifiche prove di efficacia, ma è prescrivibile a carico del SSN per il dolore neuropatico di qualsiasi origine.

sono risultate le associazioni di gabapentin e venlafaxina e gabapentin e morfina.

Nevralgia post-herpetica

E’ una condizione dolorosa che insorge do- po infezione da herpes zoster. L’età avanzata e l’intensità del dolore in fase acuta sono gli unici fattori di rischio per la nevralgia post- herpetica. Il dolore è descritto come brucian- te, lancinante, penetrante. Lo sfioramento in- duce dolore nel 90% dei casi (allodinia). I farmaci con dimostrata efficacia in questa condizione sono l’amitriptilina al dosaggio di 65-100 mg, la nortriptilina ad un dosaggio di circa 90 mg, desimipramina a 65-73 mg. Anche il gabapentin, il pregabalin ed il val- proato quest’ultimo al dosaggio di 1000 mg/die sono indicati. Trattamenti topici co- me patch di lidocaina al 5% e capsaicina to- pica 0.075% presentano un ottima azione sul dolore post-herpetico in particolare se con allodinia ed in zone dolorose poco estese. Oxicodone, morfina, metadone e tramadolo sono indicati come farmaci di seconda scelta a causa degli effetti collaterali, nonostante la notevole efficacia (19).

Nonostante le recenti scoperte sulla patoge- nesi del dolore neuropatico la gestione farma- cologica continua ad essere una sfida. I tratta- menti realmente efficaci per il dolore neuro- patico sono pochi. Un chirurgo francese del XVI secolo, Ambroise Parè, diceva “nulla è in grado di distruggere le forze quanto il dolo- re”. La conoscenza dell’anatomia e dei mecca- nismi del dolore, l’empatia con il paziente che lamenta dolore sono una sfida per il medico e per le strutture ospedaliere che dovrebbero fornire strumenti culturali per affinare l’atten- zione a questo tipo di condizione.

BIBLIOGRAFIA

(1) Adams RD, Victor M, Ropper AH. Principi di Neurologia. Frattola L, Nappi G, Tonali P Eds. McGraw Hill Libri Italia Srl, Milano 1998. Pagi- ne 123-143.

(2) Merskey H, Bogduk N. Task Force on Taxo- nomy of the International Association for the Study of Pain: Classification of Chronic Pain. Description of Pain Syndromes and Definitions

69 Neurologia

of Pain Terms. IASP Press, Seattle, WA. 1994 (3) Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neuropathic pain. Diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:1524-1534.

(4) Schwartzman RJ, Grothusen J, Kiefer TR, Rohr P. Neuropatic central pain. Arch Neurol 2001;58:1547-1550.

(5) Woolf CJ, Mannion RJ. Neuropathic pain: ae- tiology, symptoms, mechanisms, and manage- ment. Lancet 1999;353:1959-1964. Sindrup SH, Jensen TS. Effects of pharmacological treatment of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999:83;389-400. (6) Sindrup SH, Jensen TS. Effects of pharmaco- logical treatment of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999:83;389-400

(7) Woolf CJ. Dissecting out mechanisms respon- sible for peripheral neuropathic pain: implica- tions for diagnosis and therapy. Life Sci. 2004;74:2605-2610.

(8) Neurontin Full U.S. Prescribing Information. http://www.pfizer.com/download/uspi_neuron- tin.pdf

(9) Schott GH. Delayed onset and resolution of pain. Brain 2001;6:1067-1076.

(10) Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpaa M, Jorum E, Serra J, Jensen TS. EFNS guidelines on assessment of neuropathic pain and treatment. Eur J Neurol 2004;11:153-162. (11) Foley KM. Opioids and chronic neuropathic pain. N Engl J Med 2003;348:1279-1281. (12) Zimmermann M. Pathobiology of neuropa- thic pain. Eur J Pharmacol 2001;429:23-37. (13) Cooke SF, Bliss TVP. Plasticity in the human central nervous system. Brain 2006;129:1659- 1673.

(14) Baron R. Mechanisms of disease: neuropa- thic pain- a clinical perspective. R. Nat Clin Pract Neurol 2006;2:95-106.

(15) Finnerup NB, Jensen TS. Mechanisms of di- sease: mechanism-based classification of neuro- pathic pain-a critical analysis. Nat Clin Pract Neurol 2006;2:107-115.

(16) Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain 2005;118:289-305.

(17) Irving GA. Contemporary assessment and management of neuropathic pain. Neurology 2005;64:S21-27.

Murray KT. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther 2004;75:234-241.

(19) Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nutmikko T, Sampaio C, Sindrup S, Wif- fen P. EFNS guidelines on pharmacological treat- ment of neuropathic pain. Eur J Neurol 2006 Eur J Neurol 2006; 13:1153-1169.

(20) Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H; Quality Standards Subcom- mittee of the American Academy of Neurology. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quali- ty Standards Subcommittee of the American Aca- demy of Neurology. Neurology 2004;63:959-965. (21) Troels S. Jensen. Anticonvulsants in neuro- pathic pain: rationale and clinical evidence. Euro- pean Journal of Pain 2002;6 (Suppl. A): 61-68. (22) Wiffen P, Collins S, McQuay H, Carroll D, Jadad A, Moore A. Anticonvulsant drugs for acu- te and chronic pain (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

(23) Guay DR. Pregabalin in neuropathic pain: a more “pharmaceutically elegant” gabapentin? Am J Geriatr Pharmacother 2005;3:274-287. (24) McClean GJ. Intravenous infusion of pheny- toin relieves neuropathic pain: a randomized, double-blinded, placebo controlled, crossover study. Anesth Analg 1999; 89:985-988.

(25) Mason L, Moore RA, Derry S, Edwards JE, McQuay J. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004;328:991-4. (26) Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs. 2004;64:937-947.

(27) Duhmke RM, Cornblath DD, Hollingshead JRF. Tramadol for neuropathic pain (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd. (28) Uhle EI, Becker R, Gatscher S, Bertalanffy H. Continuous intrathecal clonidine administra- tion for the treatment of neuropathic pain. Ste- reotact Funct Neurosurg. 2000;75:167-175. (29) Hocking G, Cousins MJ. Ketamine in chro- nic pain management: an evidence-based review. Anesth Analg 2003;97:1730-1739.

(30) Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind pla- cebo controlled crossover trial. BMJ 2004; 329: 253-260.

(31) Rog DJ, Nurmikko TJ, Friede T, Young CA.

Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 2005;65:812-819.

(32) Kern U, Martin C, Scheicher S, Muller H. Botulinum toxin type A influences stump pain af- ter limb amputations.J Pain Symptom Manage 2003;26:1069-1070.

(33) Naumann M, Eberhardt B, Laskawi R, Por- ta M, Schnider P, Sostak P, Lutze M. Botulinum toxin in rare pain syndromes. J Neurol 2004;251 (Suppl 1):I39-I40

(34) Carroll D, Moore RA, McQuay HJ, Fair- man F, Tram?r M, Leijon G. Transcutaneous elec- trical nerve stimulation (TENS) for chronic pain (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

(35) Rollnik JD, Wustefeld S, Dauper J, Karst M, Fink M, Kossev A, Dengler R. Repetitive transcra- nial magnetic stimulation for the treatment of chro- nic pain - a pilot study. Eur Neurol. 2002;48:6-10. (36) Brown JA, Pilitsis JG. Motor cortex stimula- tion.Pain med 2006;7:S140-145.

(37) Management of Chronic Central Neuropa- thic Pain Following Traumatic Spinal Cord Inju- ry. Evidence Report/Technology Assessment Number 45. AHRQ Publication No. 01-E063 September 2001

(38) Mailis A, Furlan A. Sympathectomy for neu- ropathic pain (Cochrane Review). In: The Co- chrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

(39) Nicholson BD. Evaluation and treatment of central pain syndromes. Neurology. 2004;62 (Suppl 2):S30-36.

(40) Finnerup NB, Jensen TS. Spinal cord injury pain—mechanisms and treatment. Eur J Neurol 2004;11:73-82.

(41) Beard S, Hunn A, Wight J.Treatment for spasti- city and pain in multiple sclerosis: a systematic re- view. Heath Tecnology Assessment 2003; vol 7 N 40. (42) Colombo C, Comi G. La gestione del pa- ziente con sclerosi multipla: la fatica ed il dolore. Neuro Sci 2004;25:S443-449.

(43) Jensen TS, Lenz FA. Central post-stroke pain: a challenge for the scientist and the clinician. Pain1995;61:161-164.

(44) Hansson P. Post-stroke pain case study: cli- nical characteristics, therapeutic options and long-term follow-up. Eur J Neurol 2004;11 Suppl 1:22-30.

(45) Djaldetti R, Shifrin A, Rogowski Z, Sprecher E, Melamed E, Yarnitsky D. Quantitative measu-

rement of pain sensation in patients with Parkin- son disease. Neurology 2004;62:2171-2175. (46) Waseem S, Gwinn-Hardy K. Pain in Parkin- son’s disease. Common yet seldom recognized symptom is treatable. Postgrad Med. 2001; 110:33-4, 39-40, 46.

(47) Buzas B, Max MB. Pain in Parkinson disea- se. Neurology 2004;62:2156-2157.

(49) Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ 2006;175:265-275.

(50) Belgrade MJ. Following the clues to neuro- pathic pain. Distribution and other leads reveal the cause and the treatment approach. Postgrad Med. 1999;106:127-132, 135-140.