Limits...
Long lasting pain hypersensitivity following ligation of the tendon of the masseter muscle in rats: a model of myogenic orofacial pain.

Guo W, Wang H, Zou S, Wei F, Dubner R, Ren K - Mol Pain (2010)

Bottom Line: In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery.In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia) and CD11b (microglia) were found.The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neural and Pain Sciences, Dental School & Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA.

ABSTRACT

Background: A major subgroup of patients with temporomandibular joint (TMJ) disorders have masticatory muscle hypersensitivity. To study myofacial temporomandibular pain, a number of preclinical models have been developed to induce myogenic pain of the masseter muscle, one of the four muscles involved in mastication. The currently used models, however, generate pain that decreases over time and only lasts from hours to weeks and hence are not suitable for studying chronicity of the myogenic pain in TMJ disorders. Here we report a model of constant myogenic orofacial pain that lasts for months.

Results: The model involves unilateral ligation of the tendon of the anterior superficial part of the rat masseter muscle (TASM). The ligation of the TASM was achieved with two chromic gut (4.0) ligatures via an intraoral approach. Nocifensive behavior of the rat was assessed by probing the skin site above the TASM with a series of von Frey filaments. The response frequencies were determined and an EF50 value, defined as the von Frey filament force that produces a 50% response frequency, was derived and used as a measure of mechanical sensitivity. Following TASM ligation, the EF50 of the injured side was significantly reduced and maintained throughout the 8-week observation period, suggesting the presence of mechanical hyperalgesia/allodynia. In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery. Somatotopically relevant Fos protein expression was indentified in the subnucleus caudalis of the spinal trigeminal sensory complex. In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia) and CD11b (microglia) were found. Morphine (0.4-8 mg/kg, s.c.) and duloxetine (0.4-20 mg/kg, i.p.), a selective serotonin-norepinephrine reuptake inhibitor, produced dose-dependent attenuation of hyperalgesia.

Conclusions: Ligation injury of the TASM in rats led to long-lasting and constant mechanical hypersensitivity of myogenic origin. The model will be particularly useful in studying the chronicity of myogenic pain TMJ disorders. The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.

Show MeSH

Related in: MedlinePlus

Mechanical hyperalgesia/allodynia following ligation of the masseter tendon. The orofacial skin site above the TASM was probed with a series of von Frey microfilaments. The EF50s were derived from the respective stimulus-response frequency function curves and are plotted against time after surgery. A significant reduction of EF50 indicates increased mechanical sensitivity, or mechanical hyperalgesia and allodynia. Note log scales for the ordinate. Filled circles show group means and open circles indicate individual EF50 of the side ipsilateral to injury. Error bars are 95% confidence intervals of EF50s. a. Rats receiving ligation of the TASM (n = 14). A significant reduction of EF50 indicating significant mechanical allodynia occurred ipsilateral to injury at 3 d and was maintained through the 8-week period. There was no change in EF50 on the equivalent contralateral site. b. Sham-operated rats showed a temporary reduction of EF50 at 3 d ipsilateral to intraoral procedure (n = 14). *, p < 0.01 vs. contralateral site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2914030&req=5

Figure 2: Mechanical hyperalgesia/allodynia following ligation of the masseter tendon. The orofacial skin site above the TASM was probed with a series of von Frey microfilaments. The EF50s were derived from the respective stimulus-response frequency function curves and are plotted against time after surgery. A significant reduction of EF50 indicates increased mechanical sensitivity, or mechanical hyperalgesia and allodynia. Note log scales for the ordinate. Filled circles show group means and open circles indicate individual EF50 of the side ipsilateral to injury. Error bars are 95% confidence intervals of EF50s. a. Rats receiving ligation of the TASM (n = 14). A significant reduction of EF50 indicating significant mechanical allodynia occurred ipsilateral to injury at 3 d and was maintained through the 8-week period. There was no change in EF50 on the equivalent contralateral site. b. Sham-operated rats showed a temporary reduction of EF50 at 3 d ipsilateral to intraoral procedure (n = 14). *, p < 0.01 vs. contralateral site.

Mentions: Following TASM ligation, the EF50 of the injured side was significantly reduced (Fig. 2a), indicating the development of mechanical hyperalgesia/allodynia. The reduction of EF50 was significant (p < 0.001, n = 14) at the first test (3 d post ligation) and the hyperalgesia/allodynia maintained throughout the observation period up to 8 weeks. There were no significant changes in EF50 on the contralateral side, suggesting that the effect of ligation was limited to the site of injury. In sham-operated rats (n = 14), the EF50 on the injured side was reduced initially after surgery. The reduction of EF50 in the sham rats was smaller compared to the tendon-ligated rats and returned to the baseline level by 7-10 days. The small and short-lasting hypersensitivity after sham operation was likely due to tissue injury produced by the surgical procedure, similar to that seen in the sham operation of infraorbital nerve injury [21].


Long lasting pain hypersensitivity following ligation of the tendon of the masseter muscle in rats: a model of myogenic orofacial pain.

Guo W, Wang H, Zou S, Wei F, Dubner R, Ren K - Mol Pain (2010)

Mechanical hyperalgesia/allodynia following ligation of the masseter tendon. The orofacial skin site above the TASM was probed with a series of von Frey microfilaments. The EF50s were derived from the respective stimulus-response frequency function curves and are plotted against time after surgery. A significant reduction of EF50 indicates increased mechanical sensitivity, or mechanical hyperalgesia and allodynia. Note log scales for the ordinate. Filled circles show group means and open circles indicate individual EF50 of the side ipsilateral to injury. Error bars are 95% confidence intervals of EF50s. a. Rats receiving ligation of the TASM (n = 14). A significant reduction of EF50 indicating significant mechanical allodynia occurred ipsilateral to injury at 3 d and was maintained through the 8-week period. There was no change in EF50 on the equivalent contralateral site. b. Sham-operated rats showed a temporary reduction of EF50 at 3 d ipsilateral to intraoral procedure (n = 14). *, p < 0.01 vs. contralateral site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2914030&req=5

Figure 2: Mechanical hyperalgesia/allodynia following ligation of the masseter tendon. The orofacial skin site above the TASM was probed with a series of von Frey microfilaments. The EF50s were derived from the respective stimulus-response frequency function curves and are plotted against time after surgery. A significant reduction of EF50 indicates increased mechanical sensitivity, or mechanical hyperalgesia and allodynia. Note log scales for the ordinate. Filled circles show group means and open circles indicate individual EF50 of the side ipsilateral to injury. Error bars are 95% confidence intervals of EF50s. a. Rats receiving ligation of the TASM (n = 14). A significant reduction of EF50 indicating significant mechanical allodynia occurred ipsilateral to injury at 3 d and was maintained through the 8-week period. There was no change in EF50 on the equivalent contralateral site. b. Sham-operated rats showed a temporary reduction of EF50 at 3 d ipsilateral to intraoral procedure (n = 14). *, p < 0.01 vs. contralateral site.
Mentions: Following TASM ligation, the EF50 of the injured side was significantly reduced (Fig. 2a), indicating the development of mechanical hyperalgesia/allodynia. The reduction of EF50 was significant (p < 0.001, n = 14) at the first test (3 d post ligation) and the hyperalgesia/allodynia maintained throughout the observation period up to 8 weeks. There were no significant changes in EF50 on the contralateral side, suggesting that the effect of ligation was limited to the site of injury. In sham-operated rats (n = 14), the EF50 on the injured side was reduced initially after surgery. The reduction of EF50 in the sham rats was smaller compared to the tendon-ligated rats and returned to the baseline level by 7-10 days. The small and short-lasting hypersensitivity after sham operation was likely due to tissue injury produced by the surgical procedure, similar to that seen in the sham operation of infraorbital nerve injury [21].

Bottom Line: In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery.In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia) and CD11b (microglia) were found.The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neural and Pain Sciences, Dental School & Program in Neuroscience, University of Maryland, Baltimore, MD 21201, USA.

ABSTRACT

Background: A major subgroup of patients with temporomandibular joint (TMJ) disorders have masticatory muscle hypersensitivity. To study myofacial temporomandibular pain, a number of preclinical models have been developed to induce myogenic pain of the masseter muscle, one of the four muscles involved in mastication. The currently used models, however, generate pain that decreases over time and only lasts from hours to weeks and hence are not suitable for studying chronicity of the myogenic pain in TMJ disorders. Here we report a model of constant myogenic orofacial pain that lasts for months.

Results: The model involves unilateral ligation of the tendon of the anterior superficial part of the rat masseter muscle (TASM). The ligation of the TASM was achieved with two chromic gut (4.0) ligatures via an intraoral approach. Nocifensive behavior of the rat was assessed by probing the skin site above the TASM with a series of von Frey filaments. The response frequencies were determined and an EF50 value, defined as the von Frey filament force that produces a 50% response frequency, was derived and used as a measure of mechanical sensitivity. Following TASM ligation, the EF50 of the injured side was significantly reduced and maintained throughout the 8-week observation period, suggesting the presence of mechanical hyperalgesia/allodynia. In sham-operated rats, the EF50 of the injured side was transiently reduced for about a week, likely due to injury produced by the surgery. Somatotopically relevant Fos protein expression was indentified in the subnucleus caudalis of the spinal trigeminal sensory complex. In the same region, persistent upregulation of NMDA receptor NR1 phosphorylation and protein expression and increased expression of glial markers glial fibrillary acidic protein (astroglia) and CD11b (microglia) were found. Morphine (0.4-8 mg/kg, s.c.) and duloxetine (0.4-20 mg/kg, i.p.), a selective serotonin-norepinephrine reuptake inhibitor, produced dose-dependent attenuation of hyperalgesia.

Conclusions: Ligation injury of the TASM in rats led to long-lasting and constant mechanical hypersensitivity of myogenic origin. The model will be particularly useful in studying the chronicity of myogenic pain TMJ disorders. The model can also be adapted to other regions of the body for studying pathology of painful tendinopathy seen in sports injury, muscle overuse, and rheumatoid arthritis.

Show MeSH
Related in: MedlinePlus