Fiber Types Involved in Neuropathic Pain

Fiber Types Involved in Neuropathic Pain  Aβ fibers   Large diameter, myelinated, fast conduction velocity Mechanoreceptors normally activated by non-noxious mechanical stimuli (touch)  Aδ fibers   Medium diameter, myelinated, intermediate conduction velocity Normally activated by noxious stimuli (transmit sharp pain)  C fibers  Small diameter, unmyelinated, slow conduction velocity  Normally activated by noxious stimuli (responsible for secondary pain, normally burning, aching pain)  In neuropathic pain abnormal sensations may be transmitted along Aβ , Aδ or C fibers Dworkin Clin J Pain. 2002;18:343-349 Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4 th Ed. 1999.;11-57 Processing of pain stimulus Development of Neuropathic Pain Syndrome Symptoms Neuropathic pain Spontaneous pain Stimulus-evoked pain Pathophysiology Mechanisms Metabolic Ischemic Traumatic Toxic Infectious Immune-related Etiology Hereditary Compression Nerve damage Woolf and Mannion. Lancet 1999;353:1959-64 Neuropathic Pain: Underlying Mechanisms  Peripheral Mechanisms Central  Membrane hyperexcitability  Mechanisms  Membrane hyperexcitability  Ectopic discharges   Peripheral Ectopic discharges sensitization Wind up  Central sensitization  Denervation supersensitivity  Loss of inhibitory controls Attal N et al. Acta Neurol Scand. 1999;173:12-24. Woolf CJ et al. Lancet. 1999;353:19591964. Roberts et al. In Casey KL (Ed). Pain and central nervous system disease. 1991 Neuropathic pain in leprosy patients  The most typical symptoms of chronic neuropathic pain in treated leprosy patients are: continuous burning pain  dysesthesia  paresthesia  paroxysmal pain attacks  Hietaharju et al. 2000 Neuropathic pain in leprosy patients  Allodynia and hyperalgesia seem to be unusual phenomena in treated leprosy patients (exception: nerve abscess, chronic neuritis)  These symptoms are typical in states with well preserved and irritated peripheral sensory fibers which are overactive and cause central sensitization  Leprosy: silent inflammation and slow but complete destruction of the nerves Symptoms and related mechanisms   Paresthesia  ectopic discharges in Aβ fibres Dysesthesia  ectopic discharges in Aβ fibres ectopic discharges in C fibres  Paroxysmal shooting or lancinating pain  Symptoms and related mechanisms  Continuous burning pain peripheral nociceptor sensitization  loss of inhibitory controls  ectopic discharges in C fibres  Ectopic Discharges Injured nerve fibers develop increased expression of Na + channels Primary excitatory afferent nerve fiber Na+ channel expression increased Conduction frequency amplified Na+ = sodium ion. England et al. Neurology 1996;47:272-76. Ochoa et al. Brain. 1980;103:835-853 Taylor. Curr Pain Headache Rep. 2001;5:151-161. Sukhotinsky et al. Eur J Pain. 2004;8(2):135-43 Peripheral Sensitization Primary afferent nerve fibers NGF Dorsal horn neurons NGF NGF NGF Neuropeptide release Innocuous stimulus Pain sensation Woolf and Mannion. Lancet 1999;353:1959-1964 Loss of Inhibitory Controls Dorsal horn neuron Descending Local Normal To brain Descending Local Injured Innocuous or noxious stimulus To brain Exaggerated pain response Spontaneous firing Woolf and Mannion. Lancet 1999;353:1959-1964 Development of Neuropathic Pain Syndrome Symptoms Neuropathic pain Spontaneous pain Stimulus-evoked pain Pathophysiology Mechanisms ? ? ? Infectious Immune-related Etiology Ischemic ? Compression Nerve damage in leprosy Woolf and Mannion. Lancet 1999;353:1959-64