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

Abstract

Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Neuropathic pain is a non-nociceptive pain or "deafferentation" 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). 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. The quality of pain presents as spontaneous pain (continuous and paroxysmal), abnormal pain (allodynia, hyperalgesia, hyperpathia), paroxysmal pain. 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. 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 warranted. 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.