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The effects of a co-application of menthol and capsaicin on nociceptive behaviors of the rat on the operant orofacial pain assessment device.

Anderson EM, Jenkins AC, Caudle RM, Neubert JK - PLoS ONE (2014)

Bottom Line: When applied together though, the licks at 21°C were equal to those at 33°C and both were significantly higher than at 45°C.These results suggest that co-activation of TRP channels can reduce certain nociceptive behaviors.These data demonstrate that the motivational aspects of nociception can be influenced selectively by TRP channel modulation and that certain aspects of pain can be dissociated and therefore targeted selectively in the clinic.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, Florida, United States of America ; Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, Florida, United States of America.

ABSTRACT

Background: Transient receptor potential (TRP) cation channels are involved in the perception of hot and cold pain and are targets for pain relief in humans. We hypothesized that agonists of TRPV1 and TRPM8/TRPA1, capsaicin and menthol, would alter nociceptive behaviors in the rat, but their opposite effects on temperature detection would attenuate one another if combined.

Methods: Rats were tested on the Orofacial Pain Assessment Device (OPAD, Stoelting Co.) at three temperatures within a 17 min behavioral session (33°C, 21°C, 45°C).

Results: The lick/face ratio (L/F: reward licking events divided by the number of stimulus contacts. Each time there is a licking event a contact is being made.) is a measure of nociception on the OPAD and this was equally reduced at 45°C and 21°C suggesting they are both nociceptive and/or aversive to rats. However, rats consumed (licks) equal amounts at 33°C and 21°C but less at 45°C suggesting that heat is more nociceptive than cold at these temperatures in the orofacial pain model. When menthol and capsaicin were applied alone they both induced nociceptive behaviors like lower L/F ratios and licks. When applied together though, the licks at 21°C were equal to those at 33°C and both were significantly higher than at 45°C.

Conclusions: This suggests that the cool temperature is less nociceptive when TRPM8/TRPA1 and TRPV1 are co-activated. These results suggest that co-activation of TRP channels can reduce certain nociceptive behaviors. These data demonstrate that the motivational aspects of nociception can be influenced selectively by TRP channel modulation and that certain aspects of pain can be dissociated and therefore targeted selectively in the clinic.

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Related in: MedlinePlus

The effects of menthol on a cold 7°C temperature.(A) The Lick/Face ratio was significantly reduced by menthol application 30 mins before testing. (B) Licking behavior was also significantly reduced by menthol. (C) No effect was observed for contact behavior. A * represents a p-value of less than 0.05 with a paired t-test. N = 13 for all graphs.
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pone-0089137-g005: The effects of menthol on a cold 7°C temperature.(A) The Lick/Face ratio was significantly reduced by menthol application 30 mins before testing. (B) Licking behavior was also significantly reduced by menthol. (C) No effect was observed for contact behavior. A * represents a p-value of less than 0.05 with a paired t-test. N = 13 for all graphs.

Mentions: We had hypothesized that menthol would decrease the licking behavior at the cool temperature of 21°C, and although it did decrease, this result was not statistically significant. We examined the effects of menthol on a colder temperature of 7°C to address this unexpected result. As illustrated in Figure 5A, the Lick/Face ratio was significantly decreased by menthol at 7°C (paired t-test, t(11) = 2.966, p = 0.0128). This effect was due to a significant reduction of licking behavior 7°C (Figure 5B, paired t-test, t(11) = 2.662, p = 0.0221) demonstrating the effects of menthol on altering consumption behavior and nociception at cold temperatures on this assay. No effect was observed for contact behavior (Figure 5C, paired t-test, t(11) = 0.7766, p = 0.4538).


The effects of a co-application of menthol and capsaicin on nociceptive behaviors of the rat on the operant orofacial pain assessment device.

Anderson EM, Jenkins AC, Caudle RM, Neubert JK - PLoS ONE (2014)

The effects of menthol on a cold 7°C temperature.(A) The Lick/Face ratio was significantly reduced by menthol application 30 mins before testing. (B) Licking behavior was also significantly reduced by menthol. (C) No effect was observed for contact behavior. A * represents a p-value of less than 0.05 with a paired t-test. N = 13 for all graphs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928399&req=5

pone-0089137-g005: The effects of menthol on a cold 7°C temperature.(A) The Lick/Face ratio was significantly reduced by menthol application 30 mins before testing. (B) Licking behavior was also significantly reduced by menthol. (C) No effect was observed for contact behavior. A * represents a p-value of less than 0.05 with a paired t-test. N = 13 for all graphs.
Mentions: We had hypothesized that menthol would decrease the licking behavior at the cool temperature of 21°C, and although it did decrease, this result was not statistically significant. We examined the effects of menthol on a colder temperature of 7°C to address this unexpected result. As illustrated in Figure 5A, the Lick/Face ratio was significantly decreased by menthol at 7°C (paired t-test, t(11) = 2.966, p = 0.0128). This effect was due to a significant reduction of licking behavior 7°C (Figure 5B, paired t-test, t(11) = 2.662, p = 0.0221) demonstrating the effects of menthol on altering consumption behavior and nociception at cold temperatures on this assay. No effect was observed for contact behavior (Figure 5C, paired t-test, t(11) = 0.7766, p = 0.4538).

Bottom Line: When applied together though, the licks at 21°C were equal to those at 33°C and both were significantly higher than at 45°C.These results suggest that co-activation of TRP channels can reduce certain nociceptive behaviors.These data demonstrate that the motivational aspects of nociception can be influenced selectively by TRP channel modulation and that certain aspects of pain can be dissociated and therefore targeted selectively in the clinic.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Florida College of Dentistry, Gainesville, Florida, United States of America ; Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, Florida, United States of America.

ABSTRACT

Background: Transient receptor potential (TRP) cation channels are involved in the perception of hot and cold pain and are targets for pain relief in humans. We hypothesized that agonists of TRPV1 and TRPM8/TRPA1, capsaicin and menthol, would alter nociceptive behaviors in the rat, but their opposite effects on temperature detection would attenuate one another if combined.

Methods: Rats were tested on the Orofacial Pain Assessment Device (OPAD, Stoelting Co.) at three temperatures within a 17 min behavioral session (33°C, 21°C, 45°C).

Results: The lick/face ratio (L/F: reward licking events divided by the number of stimulus contacts. Each time there is a licking event a contact is being made.) is a measure of nociception on the OPAD and this was equally reduced at 45°C and 21°C suggesting they are both nociceptive and/or aversive to rats. However, rats consumed (licks) equal amounts at 33°C and 21°C but less at 45°C suggesting that heat is more nociceptive than cold at these temperatures in the orofacial pain model. When menthol and capsaicin were applied alone they both induced nociceptive behaviors like lower L/F ratios and licks. When applied together though, the licks at 21°C were equal to those at 33°C and both were significantly higher than at 45°C.

Conclusions: This suggests that the cool temperature is less nociceptive when TRPM8/TRPA1 and TRPV1 are co-activated. These results suggest that co-activation of TRP channels can reduce certain nociceptive behaviors. These data demonstrate that the motivational aspects of nociception can be influenced selectively by TRP channel modulation and that certain aspects of pain can be dissociated and therefore targeted selectively in the clinic.

Show MeSH
Related in: MedlinePlus