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Pharmacological Approaches to Neuropathic Pain Differential Diagnosis • • • • • Pain of dental origin Oral soft tissue pain Temporomandibular joint pain Myofascial pain dysfunction Neuropathic pain From: Bonica, “The Management of Pain”, 1990. Pain Fibers •C • A • Changes in A From: Dickinson & Fleetwood-Walker, Trends in Pharm. Sci. 20: 324, 1999. Pain of Dental Origin • Physical findings – Pulpal and periodontal pain – Mucosal and other soft tissue pain • Radiographic findings • Nature and excitatory causes of pain Treatment of Dental Pain • Operative or surgical intervention • Drug treatment –Anesthetics –NSAIDS –Opioids Temporomandibular Joint dysfunctions • Disorders of muscles of mastication(myofascial pain dysfunction) • Internal joint derangement • Degenerative joint disease • Fractures, infections, tumors Treatment of Myofascial Pain Dysfunction • Non-drug treatment • Drug treatment – NSAIDS, Opioids – Tricyclic antidepressants (amitriptyline) – Centrally-acting muscle relaxants – Glucocorticosteroids From: Bonica, “The Management of Pain”, 1990. Neuropathic Pain • Pain in absence or in addition to nociceptive component • Example – trigeminal neuralgia • Characteristics of pain From: Bonica, “The Management of Pain”, 1990. Treatment of Neuropathic Pain • Surgical • Drug therapy From: Bonica, “The Management of Pain”, 1990. Drug Therapy (Neuropathic Pain) • • • • Carbamazepine Phenytoin Baclofen Gabapentin • Tricylic antidepressants • Local anesthetics • Ketamine • Clonazepam Experimental Drug Therapy for Neuropathic Pain • • • • • • N-type calcium channel blockers 2-adrenoceptor agonists (clonidine) NMDA receptor antagonists Selective serotonin reutake inhibitors Adenosine receptor agonists Valproic acid Tricyclic Antidepressants • Inhibit reuptake of catecholamines and serotonin • Block NMDA receptors • Release endogenous opioids • Peripheral action Carbamazepine (Tegretol) • Blocks sodium channels • Increases the release of catecholamines, thus indirectly stimulating 2-adrenoceptors Baclofen (p-Chlorophenyl GABA) (Lioresal) • Inhibits the release of excitatory neurotransmitters • A GABAB receptor agonist Valproic Acid (Depakene) • Increases GABA synthesis • Blocks sodium channels • Inhibits T (low threshold) calcium channels Gabapentin (Neurontin) • Binds to Gabapentin-binding protein • Blocks calcium channels • Increases GABA synthesis • Reduces glutamate Ketamine (Ketalar) • An NMDA receptor antagonist