RESUMO
AIMS: The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). MAIN METHODS: Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 µg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. KEY FINDINGS: Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. SIGNIFICANCE: Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain.
Assuntos
Amitriptilina/uso terapêutico , Eletroacupuntura , Dor Nociceptiva/terapia , Limiar da Dor/efeitos dos fármacos , Analgésicos não Narcóticos/uso terapêutico , Animais , Terapia Combinada , Infusões Parenterais , Injeções Espinhais , Masculino , Ratos , Ratos WistarRESUMO
AIM: This study examines if injection of cobalt chloride (CoCl(2)) or antagonists of muscarinic cholinergic (atropine), µ(1)-opioid (naloxonazine) or 5-HT(1) serotonergic (methiothepin) receptors into the dorsal or ventral portions of the anterior pretectal nucleus (APtN) alters the antinociceptive effects of stimulating the retrosplenial cortex (RSC) in rats. MAIN METHOD: Changes in the nociceptive threshold were evaluated using the tail flick or incision pain tests in rats that were electrically stimulated at the RSC after the injection of saline, CoCl(2) (1 mM, 0.10 µL) or antagonists into the dorsal or ventral APtN. KEY FINDINGS: The injection of CoCl(2), naloxonazine (5 µg/0.10 µL) or methiothepin (3 µg/0.10 µL) into the dorsal APtN reduced the stimulation-produced antinociception from the RSC in the rat tail flick test. Reduction of incision pain was observed following stimulation of the RSC after the injection of the same substances into the ventral APtN. The injection of atropine (10 ng/0.10 µL) or ketanserine (5 µg/0.10 µL) into the dorsal or ventral APtN was ineffective against the antinociception resulting from RSC stimulation. SIGNIFICANCE: µ(1)-opioid- and 5-HT(1)-expressing neurons and cell processes in dorsal and ventral APtN are both implicated in the mediation of stimulation-produced antinociception from the RSC in the rat tail flick and incision pain tests, respectively.
Assuntos
Córtex Cerebral/metabolismo , Terapia por Estimulação Elétrica/métodos , Manejo da Dor/métodos , Receptores Opioides mu/metabolismo , Receptores 5-HT1 de Serotonina/metabolismo , Animais , Atropina/farmacologia , Cobalto/farmacologia , Modelos Animais de Doenças , Masculino , Metiotepina/farmacologia , Naloxona/análogos & derivados , Naloxona/farmacologia , Limiar da Dor , Ratos , Ratos Wistar , Receptores Opioides mu/efeitos dos fármacos , Receptores 5-HT1 de Serotonina/efeitos dos fármacosRESUMO
The mechanisms through which electro-acupuncture (EA) and tricyclic antidepressants produce analgesia seem to be complementary: EA inhibits the transmission of noxious messages by activating supraspinal serotonergic and noradrenergic neurons that project to the spinal cord, whereas tricyclic antidepressants affect pain transmission by inhibiting the reuptake of norepinephrine and serotonin at the spinal level. This study utilized the tail-flick test and a model of post-incision pain to compare the antihyperalgesic effects of EA at frequencies of 2 or 100 Hz in rats treated with intraperitoneal or intrathecal amitriptyline (a tricyclic antidepressant). A gradual increase in the tail-flick latency (TFL) occurred during a 20-min period of EA. A strong and long-lasting reduction in post-incision hyperalgesia was observed after stimulation; the effect after 2 Hz lasting longer than after 100-Hz EA. Intraperitoneal or intrathecal amitriptyline potentiated the increase in TFL in the early moments of 2- or 100-Hz EA, and the intensity of the antihyperalgesic effect of 100-Hz EA in both the incised and non-incised paw. In contrast, it did not significantly change the intensity of the antihyperalgesic effect of 2-Hz EA. The EA-induced antihyperalgesic effects lasted longer after intraperitoneal or intrathecal amitriptyline than after saline, with this effect of amitriptyline being more evident after 100- than after 2-Hz EA. The synergetic effect of amitriptyline and EA against post-incision pain shown here may therefore represent an alternative for prolonging the efficacy of EA in the management of post-surgical clinical pain.