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Esser MJ, Sawynok J: Acute amitriptyline in a rat model of neuropathic pain: Differential symptom and route effects

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Pain (Impact Factor: 5.84). 05/1999; 80(3):643-53. DOI: 10.1016/S0304-3959(98)00261-9
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ABSTRACT The present study was designed to determine whether amitriptyline, a prototypical tricyclic antidepressant, could produce pain relieving properties in a rat model of neuropathic pain. Nerve injury was produced by tight ligation of the lumbar 5th and 6th dorsal roots and this resulted in persistent stimulus evoked neuropathic pain symptoms (tactile allodynia and thermal hyperalgesia). Thermal hyperalgesia was measured using a focused light beam directed at the ventral surface of the paw while tactile allodynia was determined using Semmes-Weinstein monofilaments applied to the ventral surface of the paw. Amitriptyline was administered systemically (intraperitoneal), spinally (intrathecal cannula), and locally (subcutaneously) via direct injection into the dorsal surface of the paw. Following systemic administration, amitriptyline completely reversed thermal hyperalgesia (10 mg/kg) in the injured paw. Spinal administration of amitriptyline (60 microg) also produced an antihyperalgesic effect. Interestingly, local administration of amitriptyline (100 nmol) had an immediate antihyperalgesic effect that persisted for 120 min following administration. Amitriptyline had no alleviating effect against mechanical allodynia regardless of the route of administration, but curiously, produced hyperaesthesia in the contralateral paw. These results indicate that in the rat model of spinal nerve ligation, amitriptyline is effective in alleviating thermal hyperalgesia (systemically, spinally and locally) but is ineffective against mechanical allodynia. The peripheral efficacy of amitriptyline suggests the possibility of the development of cream formulations that may be able to increase the local concentration of amitriptyline without increasing the systemic dose and the subsequent occurrence of side effects.

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    • "Pharmacological Reports use of these drugs that have local analgesic effects has been proposed [9] [10] [11] [12] [13] [14], but there is little data regarding antidepressant topical coadministration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies. Tricyclic antidepressants are the most studied group of antidepressants for the treatment of neuropathic pain. "
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    ABSTRACT: The therapy of neuropathic pain may include the use of co-analgesics, such as antidepressants, however, their desired analgesic effect is associated with significant side effects. An alternative approach to this is their local administration which has been proposed, but there is little data regarding their local co-administration with morphine and the nature of the interaction between morphine and either doxepin or venlafaxine, two antidepressant drugs that have been recently used in neuropathic pain therapies.
    Pharmacological reports: PR 06/2014; 66(3):459-465. DOI:10.1016/j.pharep.2013.11.004 · 2.17 Impact Factor
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    • "The tricyclic antidepressant amitriptyline is widely used in the treatment of pain in man (Sindrup et al., 2005). In rodents, it produces behavioural consequences reported as anti-nociception in several models of neuropathic pain (Esser and Sawynok, 1999; Gerner et al., 2002; Lynch et al., 2005; Nagata et al., 2009; Su et al., 2009). Neuropathic pain is a complex chronic pain state as a consequence of tissue injury, and interest has focused recently on the possible relationship between endogenous ATP and P2X receptors (nomenclature follows Alexander et al., 2009) expressed by microglia in the parts of the dorsal horn where primary afferents terminate (McGaraughty and Jarvis, 2006). "
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    • "A previous study suggests that brain [amitriptyline] in treating depression is around 5–7 mm (Glotzbach and Preskorn, 1982). To treat pain associated peripheral neuropathy, [amitriptyline] is 2-fold lower (Esser and Sawynok, 1999). Hence, amitriptyline affinity to TrkA might be sufficient to exert its biological actions. "
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