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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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The effects of capsaicin on operant behavior.A single, representative rat's response to capsaicin during a (A) temperature ramping protocol for (B) licking behavior, (C) contact behavior, and (D) reward intake. (E) Temperature still had a significant effect on behavior with capsaicin application. The Lick/Face ratio was still lower at 45°C and 21°C than at 33°C (post-hoc tests, p<0.001 and p<0.001). (F) The number of licks was altered by temperature differently than at baseline. Licks at 33°C were higher than the other two temperatures (both p<0.001). (G) Contact behavior was no longer dependent on temperature when capsaicin was applied. An *** represents a p-value less than 0.001 for a Bonferroni's post-hoc test when comparing behavior to 33°C after a One-Way ANOVA. N = 16 for graphs E–G.
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pone-0089137-g003: The effects of capsaicin on operant behavior.A single, representative rat's response to capsaicin during a (A) temperature ramping protocol for (B) licking behavior, (C) contact behavior, and (D) reward intake. (E) Temperature still had a significant effect on behavior with capsaicin application. The Lick/Face ratio was still lower at 45°C and 21°C than at 33°C (post-hoc tests, p<0.001 and p<0.001). (F) The number of licks was altered by temperature differently than at baseline. Licks at 33°C were higher than the other two temperatures (both p<0.001). (G) Contact behavior was no longer dependent on temperature when capsaicin was applied. An *** represents a p-value less than 0.001 for a Bonferroni's post-hoc test when comparing behavior to 33°C after a One-Way ANOVA. N = 16 for graphs E–G.

Mentions: A single rat's behavior is displayed in Figure 3B–D after capsaicin application. Capsaicin altered behavior in a somewhat similar way to menthol during the ramping protocol (Figure 3A). Licks were significantly decreased for the 21°C period as compared to baseline (paired t-test, t(15) = 3.368, p = 0.0042) but not significantly altered at 45°C (Figure 3B) possibly due to a floor effect. Contacts were high for this rat as more attempts were needed at 33°C to obtain the reward (Figure 3C). The reward intake for this representative rat is displayed in Figure 3D. Capsaicin appears to have reduced the mean Lick/Face values at 33°C compared to baseline, but temperature still had a significant effect (Figure 3E) as the Lick/Face ratio was lower at 45°C and 21°C than at 33°C (p<0.001 and p<0.001). Capsaicin also reduced the number of licks (Figure 3F, F(2,15) = 25.89, p<0.0001) at 21°C substantially more than 33°C such that they were no longer significantly different from 45°C. Licks at 33°C were still higher than the other two temperatures (both p<0.001). Similar to the effects of menthol, contact behavior was no longer dependent on temperature (Figure 3G).


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 capsaicin on operant behavior.A single, representative rat's response to capsaicin during a (A) temperature ramping protocol for (B) licking behavior, (C) contact behavior, and (D) reward intake. (E) Temperature still had a significant effect on behavior with capsaicin application. The Lick/Face ratio was still lower at 45°C and 21°C than at 33°C (post-hoc tests, p<0.001 and p<0.001). (F) The number of licks was altered by temperature differently than at baseline. Licks at 33°C were higher than the other two temperatures (both p<0.001). (G) Contact behavior was no longer dependent on temperature when capsaicin was applied. An *** represents a p-value less than 0.001 for a Bonferroni's post-hoc test when comparing behavior to 33°C after a One-Way ANOVA. N = 16 for graphs E–G.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0089137-g003: The effects of capsaicin on operant behavior.A single, representative rat's response to capsaicin during a (A) temperature ramping protocol for (B) licking behavior, (C) contact behavior, and (D) reward intake. (E) Temperature still had a significant effect on behavior with capsaicin application. The Lick/Face ratio was still lower at 45°C and 21°C than at 33°C (post-hoc tests, p<0.001 and p<0.001). (F) The number of licks was altered by temperature differently than at baseline. Licks at 33°C were higher than the other two temperatures (both p<0.001). (G) Contact behavior was no longer dependent on temperature when capsaicin was applied. An *** represents a p-value less than 0.001 for a Bonferroni's post-hoc test when comparing behavior to 33°C after a One-Way ANOVA. N = 16 for graphs E–G.
Mentions: A single rat's behavior is displayed in Figure 3B–D after capsaicin application. Capsaicin altered behavior in a somewhat similar way to menthol during the ramping protocol (Figure 3A). Licks were significantly decreased for the 21°C period as compared to baseline (paired t-test, t(15) = 3.368, p = 0.0042) but not significantly altered at 45°C (Figure 3B) possibly due to a floor effect. Contacts were high for this rat as more attempts were needed at 33°C to obtain the reward (Figure 3C). The reward intake for this representative rat is displayed in Figure 3D. Capsaicin appears to have reduced the mean Lick/Face values at 33°C compared to baseline, but temperature still had a significant effect (Figure 3E) as the Lick/Face ratio was lower at 45°C and 21°C than at 33°C (p<0.001 and p<0.001). Capsaicin also reduced the number of licks (Figure 3F, F(2,15) = 25.89, p<0.0001) at 21°C substantially more than 33°C such that they were no longer significantly different from 45°C. Licks at 33°C were still higher than the other two temperatures (both p<0.001). Similar to the effects of menthol, contact behavior was no longer dependent on temperature (Figure 3G).

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