Acúfenos e hiperacusia: Sección Farmacología, mecanismos basicos

Formalin-induced long-term secondary allodynia and hyperalgesia are maintained by descending facilitation

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Mónica Ambriz-Tututi^a, Silvia L. Cruz^a, Héctor Urquiza-Marín^b and Vinicio Granados-Soto^{a, ,}

^a Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, Sede Sur, México, D.F., Mexico
^b Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, Mexico

Received 9 November 2010; 

accepted 14 February 2011. 

Available online 18 February 2011.

Abstract

This work analyzes the role of cholecystokinin (CCK) receptors, dynorphin A_1-17 and descending facilitation originated in the rostral ventromedial medulla (RVM) on secondary allodynia and hyperalgesia in formalin-injected rats.

Formalin injection (50 μl, 1%, s.c.) produced acute nociception (lasting 1 hour) and long-term secondary allodynia and hyperalgesia in ipsilateral and contralateral hind paws (lasting 1–12 days).

Once established, intra-RVM administration of lidocaine at day 6, but not at 2, reversed secondary allodynia and hyperalgesia in rats.

The injection of YM022 (CCK₂ receptor antagonist), but not lorglumide (CCK₁ receptor antagonist), into the RVM or spinal cord reversed both nociceptive behaviors.

Pre-treatment with lidocaine, lorglumide or YM022 did not prevent the development of secondary allodynia or hyperalgesia regardless the administration route.

Formalin injection increased dynorphin content in the dorsal, but not the ventral, spinal cord sections at day 6. Moreover, intrathecal administration of dynorphin antiserum reversed, but was unable to prevent, secondary allodynia and hyperalgesia in both hind paws.

These results suggest that formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms which are dependent on CCK₂ receptors located in the RVM and spinal cord.

In addition, data suggest that spinal dynorphin A_1-17 and CCK play an important role in formalin-induced secondary allodynia and hyperalgesia.

Research Highlights

►Intra-RVM injection of lidocaine and YM022 reverses secondary allodynia or hyperalgesia.
►Formalin injection increases dynorphin content in the dorsal spinal cord sections at day 6.
►Intrathecal administration of dynorphin antiserum reverses secondary allodynia and hyperalgesia ►Formalin-induced secondary allodynia and hyperalgesia are maintained by activation of descending facilitatory mechanisms.

Keywords: Descending facilitation; Secondary allodynia; Secondary hyperalgesia; Dynorphin; CCK receptors; RVM; Chronic pain

Corresponding author. Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, D.F., Mexico. Tel.: + 52 55 5483 2868; fax: + 52 55 5483 2863. 

 

Fuente: Pharmacology Biochemistry and Behavior

doi:10.1016/j.pbb.2011.02.012 |