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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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Orofacial operant behavioral outcomes at cooling temperatures in sham and ION-CCI rats. A) Left image shows that a sham rat was drinking milk while its cheeks contacted the thermal module. Middle and right images show that an ION-CCI (chronic constrictive nerve-injury induced by infraorbital nerve ligation) rat was biting the thermal module (middle) or reaching the nipple of the milk bottle with its front paw. The thermal module was set at 17 °C. B&C) Two sample traces show the automatic recordings of drinking behavior in a testing period of 10 min in a sham rat (B) and an ION-CCI rat (C). The thermal module was set at 17 °C in both B and C. Orofacial contacts were indicated by “on” and withdraws indicated by “off”. D&E) Summary of total contact time (D) and total contact number (E) in sham (open bars, n=7) and ION-CCI group (solid bars, n=7). The orofacial operant tests were performed with thermal module set at 24 °C, 17 °C, and 12 °C. Rats were tested during the postoperative period of 2 weeks to 6 weeks. Data represent Mean ± SEM; * p<0.05; ** p<0.01.
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Figure 1: Orofacial operant behavioral outcomes at cooling temperatures in sham and ION-CCI rats. A) Left image shows that a sham rat was drinking milk while its cheeks contacted the thermal module. Middle and right images show that an ION-CCI (chronic constrictive nerve-injury induced by infraorbital nerve ligation) rat was biting the thermal module (middle) or reaching the nipple of the milk bottle with its front paw. The thermal module was set at 17 °C. B&C) Two sample traces show the automatic recordings of drinking behavior in a testing period of 10 min in a sham rat (B) and an ION-CCI rat (C). The thermal module was set at 17 °C in both B and C. Orofacial contacts were indicated by “on” and withdraws indicated by “off”. D&E) Summary of total contact time (D) and total contact number (E) in sham (open bars, n=7) and ION-CCI group (solid bars, n=7). The orofacial operant tests were performed with thermal module set at 24 °C, 17 °C, and 12 °C. Rats were tested during the postoperative period of 2 weeks to 6 weeks. Data represent Mean ± SEM; * p<0.05; ** p<0.01.

Mentions: Orofacial operant tests were performed in both sham and ION-CCI groups to determine if chronic trigeminal nerve injury resulted in behavioral hypersensitivity to cooling temperatures. The thermal module was set at 24°C (neutral temperature), 17°C (cooling temperature), or 12°C (noxious cold). Figure 1A illustrates some noticeable differences in orofacial operant behaviors between sham (Figure 1A left) and ION-CCI rats (Figure 1A middle and right) at the cooling temperature of 17°C. Sham rats could contact the cooling thermal module with their cheeks for a long period of time while they were licking the nipple of the milk bottle (Figure 1A left, Figure 1B). In contrast, ION-CCI rats avoided prolonged contacts to the cooling thermal module with their cheeks, and the duration of each contact was usually brief at 17°C (Figure 1C). Sometimes, ION-CCI rats tried to bite off the thermal module with their teeth (Figure 1A middle) or tried to use their front paws to obtain milk from the nipple of the drinking bottle (Figure 1A right), but they gave up these behaviors shortly after a few attempts. Figure 1D compared total contact time between sham and ION-CCI groups at different temperatures. There was no significant difference in total contact time between sham group (352±10.3 s, n=7) and ION-CCI group (301.5±41.4 s, n=7) at 24°C. However, the total contact time was significantly shorter in ION-CCI rats (204.9±27.2 s, n=7) than in sham rats (313.4±11.4 s, n=7, p<0.05) at 17°C. At 12°C, the total contact time was also significantly shorter in ION-CCI rats (61.2±4.1 s, n=7) than in sham rats (229.6±20.7 s, n=7, p<0.01). We did not observe a significant difference in total contact number between these two groups at the three testing temperatures.


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)

Orofacial operant behavioral outcomes at cooling temperatures in sham and ION-CCI rats. A) Left image shows that a sham rat was drinking milk while its cheeks contacted the thermal module. Middle and right images show that an ION-CCI (chronic constrictive nerve-injury induced by infraorbital nerve ligation) rat was biting the thermal module (middle) or reaching the nipple of the milk bottle with its front paw. The thermal module was set at 17 °C. B&C) Two sample traces show the automatic recordings of drinking behavior in a testing period of 10 min in a sham rat (B) and an ION-CCI rat (C). The thermal module was set at 17 °C in both B and C. Orofacial contacts were indicated by “on” and withdraws indicated by “off”. D&E) Summary of total contact time (D) and total contact number (E) in sham (open bars, n=7) and ION-CCI group (solid bars, n=7). The orofacial operant tests were performed with thermal module set at 24 °C, 17 °C, and 12 °C. Rats were tested during the postoperative period of 2 weeks to 6 weeks. Data represent Mean ± SEM; * p<0.05; ** p<0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Orofacial operant behavioral outcomes at cooling temperatures in sham and ION-CCI rats. A) Left image shows that a sham rat was drinking milk while its cheeks contacted the thermal module. Middle and right images show that an ION-CCI (chronic constrictive nerve-injury induced by infraorbital nerve ligation) rat was biting the thermal module (middle) or reaching the nipple of the milk bottle with its front paw. The thermal module was set at 17 °C. B&C) Two sample traces show the automatic recordings of drinking behavior in a testing period of 10 min in a sham rat (B) and an ION-CCI rat (C). The thermal module was set at 17 °C in both B and C. Orofacial contacts were indicated by “on” and withdraws indicated by “off”. D&E) Summary of total contact time (D) and total contact number (E) in sham (open bars, n=7) and ION-CCI group (solid bars, n=7). The orofacial operant tests were performed with thermal module set at 24 °C, 17 °C, and 12 °C. Rats were tested during the postoperative period of 2 weeks to 6 weeks. Data represent Mean ± SEM; * p<0.05; ** p<0.01.
Mentions: Orofacial operant tests were performed in both sham and ION-CCI groups to determine if chronic trigeminal nerve injury resulted in behavioral hypersensitivity to cooling temperatures. The thermal module was set at 24°C (neutral temperature), 17°C (cooling temperature), or 12°C (noxious cold). Figure 1A illustrates some noticeable differences in orofacial operant behaviors between sham (Figure 1A left) and ION-CCI rats (Figure 1A middle and right) at the cooling temperature of 17°C. Sham rats could contact the cooling thermal module with their cheeks for a long period of time while they were licking the nipple of the milk bottle (Figure 1A left, Figure 1B). In contrast, ION-CCI rats avoided prolonged contacts to the cooling thermal module with their cheeks, and the duration of each contact was usually brief at 17°C (Figure 1C). Sometimes, ION-CCI rats tried to bite off the thermal module with their teeth (Figure 1A middle) or tried to use their front paws to obtain milk from the nipple of the drinking bottle (Figure 1A right), but they gave up these behaviors shortly after a few attempts. Figure 1D compared total contact time between sham and ION-CCI groups at different temperatures. There was no significant difference in total contact time between sham group (352±10.3 s, n=7) and ION-CCI group (301.5±41.4 s, n=7) at 24°C. However, the total contact time was significantly shorter in ION-CCI rats (204.9±27.2 s, n=7) than in sham rats (313.4±11.4 s, n=7, p<0.05) at 17°C. At 12°C, the total contact time was also significantly shorter in ION-CCI rats (61.2±4.1 s, n=7) than in sham rats (229.6±20.7 s, n=7, p<0.01). We did not observe a significant difference in total contact number between these two groups at the three testing temperatures.

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