TY - JOUR
T1 - Role of peripheral and spinal 5-HT 3 receptors in development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia
AU - Bravo-Hernández, Mariana
AU - Cervantes-Durán, Claudia
AU - Pineda-Farias, Jorge Baruch
AU - Barragán-Iglesias, Paulino
AU - López-Sánchez, Pedro
AU - Granados-Soto, Vinicio
N1 - Funding Information:
Authors greatly appreciate the technical and bibliographical assistance of Guadalupe C. Vidal-Cantú and Héctor Vazquez, respectively. Mariana Bravo-Hernández, Claudia Cervantes-Durán, Paulino Barragán-Iglesias and Jorge B. Pineda-Farias are Conacyt fellows. This work is part of the M.Sc. dissertation of Mariana Bravo-Hernández. Partially supported by IPN , grant SIP 20110124 (PL-S).
PY - 2012/4
Y1 - 2012/4
N2 - The role of peripheral and spinal 5-HT 3 receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In experiments where the test drug was anticipated to augment or antagonize the response, 0.5 or 1% formalin, respectively, was used for injection. Peripheral ipsilateral, but not contralateral, pre-treatment (- 10 min) with serotonin (5-HT, 10-100 nmol/paw) and the selective 5-HT 3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG, 10-300 nmol/paw) increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. Moreover, spinal pre-treatment with m-CPBG (10-300 nmol/rat) increased 0.5% formalin-induced secondary hyperalgesia but not allodynia in both paws. Accordingly, peripheral ipsilateral (30-300 nmol/paw), but not contralateral (300 nmol/paw), and spinal (10-100 nmol) pre-treatment with the selective 5-HT 3 receptor antagonist ondansetron prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. The peripheral pronociceptive effects of 5-HT (100 nmol/paw) and m-CPBG (300 nmol/paw) as well as the spinal effect of m-CPBG (300 nmol/rat) were completely prevented by the peripheral (10 nmol/paw) and spinal (1 nmol/rat) injection, respectively, of ondansetron. At these doses, ondansetron did not modify per se formalin-induced nociceptive behaviors. Spinal (30-300 nmol/rat), but not peripheral (300 nmol/paw), post-treatment (on day 6) with ondansetron reversed established formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT 3 receptors participates in the development of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. In addition, our data suggest that spinal 5-HT 3 receptors play an important role during development and maintenance of these evoked long-term behaviors.
AB - The role of peripheral and spinal 5-HT 3 receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In experiments where the test drug was anticipated to augment or antagonize the response, 0.5 or 1% formalin, respectively, was used for injection. Peripheral ipsilateral, but not contralateral, pre-treatment (- 10 min) with serotonin (5-HT, 10-100 nmol/paw) and the selective 5-HT 3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG, 10-300 nmol/paw) increased 0.5% formalin-induced secondary allodynia and hyperalgesia in both paws. Moreover, spinal pre-treatment with m-CPBG (10-300 nmol/rat) increased 0.5% formalin-induced secondary hyperalgesia but not allodynia in both paws. Accordingly, peripheral ipsilateral (30-300 nmol/paw), but not contralateral (300 nmol/paw), and spinal (10-100 nmol) pre-treatment with the selective 5-HT 3 receptor antagonist ondansetron prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. The peripheral pronociceptive effects of 5-HT (100 nmol/paw) and m-CPBG (300 nmol/paw) as well as the spinal effect of m-CPBG (300 nmol/rat) were completely prevented by the peripheral (10 nmol/paw) and spinal (1 nmol/rat) injection, respectively, of ondansetron. At these doses, ondansetron did not modify per se formalin-induced nociceptive behaviors. Spinal (30-300 nmol/rat), but not peripheral (300 nmol/paw), post-treatment (on day 6) with ondansetron reversed established formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT 3 receptors participates in the development of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. In addition, our data suggest that spinal 5-HT 3 receptors play an important role during development and maintenance of these evoked long-term behaviors.
KW - 5-HT receptors
KW - Chronic pain
KW - Secondary allodynia
KW - Secondary hyperalgesia
UR - http://www.scopus.com/inward/record.url?scp=84856589320&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2012.01.013
DO - 10.1016/j.pbb.2012.01.013
M3 - Artículo
C2 - 22289689
SN - 0091-3057
VL - 101
SP - 246
EP - 257
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -