Involvement of cholecystokinin in peripheral nociceptive sensitization during diabetes in rats as revealed by the formalin response

Isela E. Juárez-Rojop, Vinicio Granados-Soto, Juan C. Díaz-Zagoya, Francisco J. Flores-Murrieta, Jorge E. Torres-López

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Abstract

The possible pronociceptive role of peripheral cholecystokinin (CCK-8) as well as CCKA and CCKB receptors in diabetic rats was assessed. Subcutaneous injection of 0.5% formalin induced a greater nociceptive behavior in diabetic than in non-diabetic rats. Moreover, local peripheral injection of CCK-8 (0.1-100 μg) significantly increased 0.5% formalin-induced nociceptive activity in diabetic, but not in non-diabetic, rats. This effect was restricted to the formalin-injected paw as administration of CCK-8 into the contralateral paw was ineffective. Local peripheral administration of CCK-8, in the absence of formalin injection, produced a low level of, but significant increase in, flinching behavior in diabetic compared to non-diabetic rats. In addition, local peripheral administration of the non-selective CCK receptor antagonist proglumide (1-100 μg), CCKA receptor antagonist lorglumide (0.1-100 μg) or CCKB receptor antagonist CR-2945 (0.1-100 μg), but not vehicle or contralateral administration of CCK receptor antagonists, significantly reduced 0.5% formalin-induced flinching in diabetic rats. CR-2945 was the most effective drug in this condition. These effects were not observed in non-diabetic rats. The local peripheral pronociceptive effect of CCK-8 (100 μg) was significantly reduced by proglumide (100 μg), lorglumide (100 μg), and CR-2945 (100 μg). Results suggest that diabetes-induced peripheral sensitization could be due to a local peripheral release of CCK-8, which in turn would act on CCKB, mainly but also in CCKA, receptors located on the primary afferent neurons. © 2006 International Association for the Study of Pain.
Original languageAmerican English
Pages (from-to)118-125
Number of pages105
JournalPain
DOIs
StatePublished - 1 May 2006

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Sincalide
Cholecystokinin
Formaldehyde
Proglumide
Cholecystokinin Receptors
Afferent Neurons
Injections
Subcutaneous Injections
Pharmaceutical Preparations
CR 2945

Cite this

Juárez-Rojop, Isela E. ; Granados-Soto, Vinicio ; Díaz-Zagoya, Juan C. ; Flores-Murrieta, Francisco J. ; Torres-López, Jorge E. / Involvement of cholecystokinin in peripheral nociceptive sensitization during diabetes in rats as revealed by the formalin response. In: Pain. 2006 ; pp. 118-125.
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abstract = "The possible pronociceptive role of peripheral cholecystokinin (CCK-8) as well as CCKA and CCKB receptors in diabetic rats was assessed. Subcutaneous injection of 0.5{\%} formalin induced a greater nociceptive behavior in diabetic than in non-diabetic rats. Moreover, local peripheral injection of CCK-8 (0.1-100 μg) significantly increased 0.5{\%} formalin-induced nociceptive activity in diabetic, but not in non-diabetic, rats. This effect was restricted to the formalin-injected paw as administration of CCK-8 into the contralateral paw was ineffective. Local peripheral administration of CCK-8, in the absence of formalin injection, produced a low level of, but significant increase in, flinching behavior in diabetic compared to non-diabetic rats. In addition, local peripheral administration of the non-selective CCK receptor antagonist proglumide (1-100 μg), CCKA receptor antagonist lorglumide (0.1-100 μg) or CCKB receptor antagonist CR-2945 (0.1-100 μg), but not vehicle or contralateral administration of CCK receptor antagonists, significantly reduced 0.5{\%} formalin-induced flinching in diabetic rats. CR-2945 was the most effective drug in this condition. These effects were not observed in non-diabetic rats. The local peripheral pronociceptive effect of CCK-8 (100 μg) was significantly reduced by proglumide (100 μg), lorglumide (100 μg), and CR-2945 (100 μg). Results suggest that diabetes-induced peripheral sensitization could be due to a local peripheral release of CCK-8, which in turn would act on CCKB, mainly but also in CCKA, receptors located on the primary afferent neurons. {\circledC} 2006 International Association for the Study of Pain.",
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Involvement of cholecystokinin in peripheral nociceptive sensitization during diabetes in rats as revealed by the formalin response. / Juárez-Rojop, Isela E.; Granados-Soto, Vinicio; Díaz-Zagoya, Juan C.; Flores-Murrieta, Francisco J.; Torres-López, Jorge E.

In: Pain, 01.05.2006, p. 118-125.

Research output: Contribution to journalArticle

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AU - Juárez-Rojop, Isela E.

AU - Granados-Soto, Vinicio

AU - Díaz-Zagoya, Juan C.

AU - Flores-Murrieta, Francisco J.

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N2 - The possible pronociceptive role of peripheral cholecystokinin (CCK-8) as well as CCKA and CCKB receptors in diabetic rats was assessed. Subcutaneous injection of 0.5% formalin induced a greater nociceptive behavior in diabetic than in non-diabetic rats. Moreover, local peripheral injection of CCK-8 (0.1-100 μg) significantly increased 0.5% formalin-induced nociceptive activity in diabetic, but not in non-diabetic, rats. This effect was restricted to the formalin-injected paw as administration of CCK-8 into the contralateral paw was ineffective. Local peripheral administration of CCK-8, in the absence of formalin injection, produced a low level of, but significant increase in, flinching behavior in diabetic compared to non-diabetic rats. In addition, local peripheral administration of the non-selective CCK receptor antagonist proglumide (1-100 μg), CCKA receptor antagonist lorglumide (0.1-100 μg) or CCKB receptor antagonist CR-2945 (0.1-100 μg), but not vehicle or contralateral administration of CCK receptor antagonists, significantly reduced 0.5% formalin-induced flinching in diabetic rats. CR-2945 was the most effective drug in this condition. These effects were not observed in non-diabetic rats. The local peripheral pronociceptive effect of CCK-8 (100 μg) was significantly reduced by proglumide (100 μg), lorglumide (100 μg), and CR-2945 (100 μg). Results suggest that diabetes-induced peripheral sensitization could be due to a local peripheral release of CCK-8, which in turn would act on CCKB, mainly but also in CCKA, receptors located on the primary afferent neurons. © 2006 International Association for the Study of Pain.

AB - The possible pronociceptive role of peripheral cholecystokinin (CCK-8) as well as CCKA and CCKB receptors in diabetic rats was assessed. Subcutaneous injection of 0.5% formalin induced a greater nociceptive behavior in diabetic than in non-diabetic rats. Moreover, local peripheral injection of CCK-8 (0.1-100 μg) significantly increased 0.5% formalin-induced nociceptive activity in diabetic, but not in non-diabetic, rats. This effect was restricted to the formalin-injected paw as administration of CCK-8 into the contralateral paw was ineffective. Local peripheral administration of CCK-8, in the absence of formalin injection, produced a low level of, but significant increase in, flinching behavior in diabetic compared to non-diabetic rats. In addition, local peripheral administration of the non-selective CCK receptor antagonist proglumide (1-100 μg), CCKA receptor antagonist lorglumide (0.1-100 μg) or CCKB receptor antagonist CR-2945 (0.1-100 μg), but not vehicle or contralateral administration of CCK receptor antagonists, significantly reduced 0.5% formalin-induced flinching in diabetic rats. CR-2945 was the most effective drug in this condition. These effects were not observed in non-diabetic rats. The local peripheral pronociceptive effect of CCK-8 (100 μg) was significantly reduced by proglumide (100 μg), lorglumide (100 μg), and CR-2945 (100 μg). Results suggest that diabetes-induced peripheral sensitization could be due to a local peripheral release of CCK-8, which in turn would act on CCKB, mainly but also in CCKA, receptors located on the primary afferent neurons. © 2006 International Association for the Study of Pain.

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