Neuropathic pain due to malignancy: Mechanisms, clinical manifestations and therapy

Abstract

Introduction Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Definition Neuropathic pain is a non-nociceptive pain or "differentiation" pain, which suggests abnormal production of impulses by neural tissue that is separated from afferent input. Impulses arise from the peripheral nervous system or central nervous system. Causes of neuropathic pain due to malignancy Neuropathic pain is caused directly by cancer-related pathology (compression/infiltration of nerve tissue, combination of compression/infiltration) or by diagnostic and therapeutic procedures (surgical procedures, chemotherapy, radiotherapy). Mechanisms Pathophysiological mechanisms are very complex and still not clear enough. Neuropathic pain is generated by electrical hyperactivity of neurons along the pain pathways. Peripheral mechanisms (primary sensitization of nerve endings, ectopically generated action potentials within damaged nerves, abnormal electrogenesis within sensory ganglia) and central mechanisms (loss of input from peripheral nociceptors into dorsal horn, aberrant sprouting within dorsal horn, central sensitization, loss of inhibitory interneurons, mechanisms at higher centers) are involved. Diagnosis The quality of pain presents as spontaneous pain (continuous and paroxysmal), abnormal pain (allodynia, hyperalgesia, hyperpathia), paroxysmal pain. Clinical manifestations Clinically, neuropathic pain is described as the pain in the peripheral nerve (cranial nerves, other mononeuropathies, radiculopathy, plexopathy, paraneoplastic peripheral neuropathy) and relatively infrequent, central pain syndrome. Therapy Treatment of neuropathic pain remains a challenge for clinicians, because there is no accepted algorithm for analgesic treatment of neuropathic pain. Pharmacotherapy is considered to be the first line therapy. Opioids combined with non-steroidal antiinflammatory drugs are warrented. If patient is relatively unresponsive to an opioid, a trial with adjuvant analgesics might be considered. Tricyclic antidepressants might be selected for patients with continuous dysesthesia, and anticonvulsants might be used if the pain is predominanty lancinating or paroxysmal. The complexity of neuropathic syndromes and underlying etiologic mechanisms warrant clinical trials to determine appropriate treatment.Tokom poslednje dekade, neuropatski bol, klinicki i eksperimentalno, siroko je istrazivan. Ucestalost neuropatskog bola kod maligniteta, rezistentnost na uobicajene tretmane, raznolikost tretmana i njihova nepredvidiva efikasnost, cine da neuropatski bol predstavlja terapijski izazov. Kod maligniteta, neuropatski bol nastaje zbog: kompresije ili infiltracije nervnog tkiva, kombinacije kompresije i infiltracije, sekundarnog nervnog ostecenja (operativne procedure, hemoterapija, radioterapija). Mehanizmi neuropatskog bola vrlo su kompleksni, mogu biti posledica lezije ili poremecaja funkcije perifernog ili centralnog nervnog sistema ili mesavine oba. Dijagnoza bolne neuropatije bazira se na ispoljavanju spontanih ili evociranih senzornih abnormalnosti, dizestezija, alodinije, hiperalgezije i hiperpatije u regiji ostecenog nerva, pleksusa, nervnog korena ili centralnih nervnih puteva. Farmakoterapija je sustinski pristup u tretmanu neuropatskih bolnih stanja. Ne postoji prihvatljivi vodic, koji bi u izboru lekova, na bazi cinjenica, bio primenjivan. Opioidi su i dalje kontroverzni, a nesteroidno-antiinflamatorni lekovi cesto korisni u kombinaciji sa opioidima. Adjuvantni analgetici upotrebljavaju se najcesce u kombinaciji sa nekim od primarnih analgetika; triciklicni antidepresanti, u kontroli "pekuceg" bola, antikonvulzanti kod neuropatskog bola neuralgicnog tipa sa "probadanjem", "cepanjem". Upotreba ne samo ovih, vec i drugih analgetika (oralni lokalni anestetici, ketamin, adenozin, magnezijum, kapsaicin) i analgetickih metoda (simpaticka i epiduralna blokada), nisu dali zadovoljavajuce rezultate. Podrzava se kombinovana terapija bazirana na multiplim farmakoloskim ciljevima i minimalnim terapijskim dozama, jer smanjuje, ne samo neuropatski bol, vec i nuzefekte.