TY - JOUR
T1 - Role of peripheral 5-HT4, 5-HT6, and 5-HT7 receptors in development and maintenance of secondary mechanical allodynia and hyperalgesia
AU - Godínez-Chaparro, Beatriz
AU - Barragán-Iglesias, Paulino
AU - Castañeda-Corral, Gabriela
AU - Rocha-González, Héctor I.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
The authors appreciate the technical and bibliographical assistance of Guadalupe C. Vidal-Cantú and Héctor Vazquez, respectively. Beatriz Godínez-Chaparro, Héctor I. Rocha-González, Paulino Barragán-Iglesias, and Gabriela Castañeda-Corral are Conacyt fellows. This work is part of the PhD dissertation of Beatriz Godínez-Chaparro; partially supported by Conacyt, Grant 59879 (VG-S).
PY - 2011/3
Y1 - 2011/3
N2 - The role of 5-hydroxytryptamine (5-HT)4, 5-HT6, and 5-HT7 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. Pretreatment (-10 min) with cromoglycate (195-1950 nmol/paw) partially inhibited acute nociceptive behaviors and completely prevented secondary allodynia and hyperalgesia on day 6 after injection. Ipsilateral peripheral pretreatment with the selective 5-HT4 (ML-10302, 1-100 nmol/paw), 5-HT6 (EMD-386088, 0.001-0.01 nmol/paw), and 5-HT7 (LP-12, 0.01-100 nmol/paw) receptor agonists significantly increased secondary allodynia and hyperalgesia in both paws. In contrast, ipsilateral peripheral pretreatment with the selective 5-HT4 (GR-125487, 1-100 nmol/paw), 5-HT6 (SB-258585, 0.00001-0.001 nmol/paw), and 5-HT7 (SB-269970, 0.1-10 nmol/paw) receptor antagonists significantly prevented formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of ML-10302 (100 nmol/paw), EMD-386088 (0.01 nmol/paw), and LP-12 (100 nmol/paw) were completely prevented by GR-125487 (5-HT4 antagonist, 1 nmol/paw), SB-258585 (5-HT 6 antagonist, 0.00001 nmol/paw), and SB-269970 (5-HT7, antagonist, 0.01 nmol/paw), respectively. Ipsilateral peripheral posttreatment with cromoglycate or GR-125487 (1-100 nmol/paw), SB-258585 (0.001-0.1 nmol/paw), and SB-269970 (0.1-10 nmol/paw) reversed formalin-induced secondary allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT4, 5-HT6, and 5-HT 7 receptors participate in the development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. 5-hydroxytryptamine (5-HT) released in peripheral tissues after formalin injection sensitized primary afferent neurons via 5-HT4, 5-HT 6, and 5-HT7 receptors, leading to development and maintenance of secondary allodynia and hyperalgesia.
AB - The role of 5-hydroxytryptamine (5-HT)4, 5-HT6, and 5-HT7 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. Pretreatment (-10 min) with cromoglycate (195-1950 nmol/paw) partially inhibited acute nociceptive behaviors and completely prevented secondary allodynia and hyperalgesia on day 6 after injection. Ipsilateral peripheral pretreatment with the selective 5-HT4 (ML-10302, 1-100 nmol/paw), 5-HT6 (EMD-386088, 0.001-0.01 nmol/paw), and 5-HT7 (LP-12, 0.01-100 nmol/paw) receptor agonists significantly increased secondary allodynia and hyperalgesia in both paws. In contrast, ipsilateral peripheral pretreatment with the selective 5-HT4 (GR-125487, 1-100 nmol/paw), 5-HT6 (SB-258585, 0.00001-0.001 nmol/paw), and 5-HT7 (SB-269970, 0.1-10 nmol/paw) receptor antagonists significantly prevented formalin-induced secondary allodynia and hyperalgesia in both paws. The pronociceptive effect of ML-10302 (100 nmol/paw), EMD-386088 (0.01 nmol/paw), and LP-12 (100 nmol/paw) were completely prevented by GR-125487 (5-HT4 antagonist, 1 nmol/paw), SB-258585 (5-HT 6 antagonist, 0.00001 nmol/paw), and SB-269970 (5-HT7, antagonist, 0.01 nmol/paw), respectively. Ipsilateral peripheral posttreatment with cromoglycate or GR-125487 (1-100 nmol/paw), SB-258585 (0.001-0.1 nmol/paw), and SB-269970 (0.1-10 nmol/paw) reversed formalin-induced secondary allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT4, 5-HT6, and 5-HT 7 receptors participate in the development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. 5-hydroxytryptamine (5-HT) released in peripheral tissues after formalin injection sensitized primary afferent neurons via 5-HT4, 5-HT 6, and 5-HT7 receptors, leading to development and maintenance of secondary allodynia and hyperalgesia.
KW - 5-HT receptors
KW - Chronic pain
KW - Secondary allodynia
KW - Secondary hyperalgesia
UR - http://www.scopus.com/inward/record.url?scp=79851514351&partnerID=8YFLogxK
U2 - 10.1016/j.pain.2010.12.020
DO - 10.1016/j.pain.2010.12.020
M3 - Artículo
C2 - 21239110
SN - 0304-3959
VL - 152
SP - 687
EP - 697
JO - Pain
JF - Pain
IS - 3
ER -