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Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine.

Zuo X, Ling JX, Xu GY, Gu JG - Mol Pain (2013)

Bottom Line: In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI).Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded.The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA.

ABSTRACT
Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

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Modification of orofacial operant behaviors by menthol at cooling temperatures. A) Total contact time in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). B) Total contact number in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). C) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). D) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). Thermal module was set at 17 °C in A to D. E&F) Same as C&D respectively except thermal module was set at 24 °C. Data represent Mean ± SEM; * p<0.05.
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Figure 2: Modification of orofacial operant behaviors by menthol at cooling temperatures. A) Total contact time in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). B) Total contact number in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). C) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). D) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). Thermal module was set at 17 °C in A to D. E&F) Same as C&D respectively except thermal module was set at 24 °C. Data represent Mean ± SEM; * p<0.05.

Mentions: We determined effects of menthol on orofacial operant behaviors in ION-CCI rats to see if cold hypersensitivity could be further exacerbated by the TRPM8 agonist. Menthol (10%) or vehicle was delivered by subcutaneous injection (150 μl) into the cheeks of the testing animals; the dose and route of menthol administration were based on a previous study in normal rats [27]. In comparison with vehicle control, menthol administration to orofacial regions of ION-CCI rats resulted in a significant reduction of total contact time (Figure 2A) in orofacial operant tests at 17°C; the total contact time was 153.7±48.4 s (n=7) with vehicle injection and reduced to 37.7±9.4 s (n=7) with menthol injection (Figure 2A). Total contact number was examined and ION-CCI rats showed significantly higher total contact number following the administration of menthol (94.3±26.7, n=7) than that following vehicle injection (40.0±8.9, n=7, P<0.05) (Figure 2B).


Operant behavioral responses to orofacial cold stimuli in rats with chronic constrictive trigeminal nerve injury: effects of menthol and capsazepine.

Zuo X, Ling JX, Xu GY, Gu JG - Mol Pain (2013)

Modification of orofacial operant behaviors by menthol at cooling temperatures. A) Total contact time in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). B) Total contact number in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). C) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). D) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). Thermal module was set at 17 °C in A to D. E&F) Same as C&D respectively except thermal module was set at 24 °C. Data represent Mean ± SEM; * p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750444&req=5

Figure 2: Modification of orofacial operant behaviors by menthol at cooling temperatures. A) Total contact time in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). B) Total contact number in ION-CCI rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). C) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). D) Total contact time in sham rats following the administration of vehicle (open bar, n=7) and menthol (solid bar, n=7). Thermal module was set at 17 °C in A to D. E&F) Same as C&D respectively except thermal module was set at 24 °C. Data represent Mean ± SEM; * p<0.05.
Mentions: We determined effects of menthol on orofacial operant behaviors in ION-CCI rats to see if cold hypersensitivity could be further exacerbated by the TRPM8 agonist. Menthol (10%) or vehicle was delivered by subcutaneous injection (150 μl) into the cheeks of the testing animals; the dose and route of menthol administration were based on a previous study in normal rats [27]. In comparison with vehicle control, menthol administration to orofacial regions of ION-CCI rats resulted in a significant reduction of total contact time (Figure 2A) in orofacial operant tests at 17°C; the total contact time was 153.7±48.4 s (n=7) with vehicle injection and reduced to 37.7±9.4 s (n=7) with menthol injection (Figure 2A). Total contact number was examined and ION-CCI rats showed significantly higher total contact number following the administration of menthol (94.3±26.7, n=7) than that following vehicle injection (40.0±8.9, n=7, P<0.05) (Figure 2B).

Bottom Line: In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI).Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded.The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA.

ABSTRACT
Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.

Show MeSH
Related in: MedlinePlus