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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.

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Effects of morphine and duloxetine on EF50s of rats at 8 weeks after ligation of the TASM. The EF50s were below 1 g prior to administration of drugs, indicating the presence of mechanical allodynia. a. Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). Morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). b. Duloxetine was injected i.p. at 0.4, 4, 10 and 20 mg/kg (1 ml/kg, n = 5 per dose). Administration of duloxetine produced significant and dose-dependent increases in EF50s tested at 60 min after injection (ANOVA, P < 0.01).
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Figure 7: Effects of morphine and duloxetine on EF50s of rats at 8 weeks after ligation of the TASM. The EF50s were below 1 g prior to administration of drugs, indicating the presence of mechanical allodynia. a. Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). Morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). b. Duloxetine was injected i.p. at 0.4, 4, 10 and 20 mg/kg (1 ml/kg, n = 5 per dose). Administration of duloxetine produced significant and dose-dependent increases in EF50s tested at 60 min after injection (ANOVA, P < 0.01).

Mentions: We finally verified the sensitivity of the TASM injury model to morphine and duloxetine, the two agents that are clinically used as analgesics and commonly used in preclinical studies [28,29]. The effects of morphine and duloxetine were evaluated in rats at 8 weeks after ligation of the TASM when persistent mechanical hyperalgesia/allodynia had developed (Fig. 2a). Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). As shown in Fig. 7a, subcutaneous administration of morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). Compared to pre-morphine EF50 of 0.45 g (95% confidence interval: 0.38-0.53 g), 4 mg/kg of morphine elevated EF50 to 20.9 g (13.1-33.4 g) (p < 0.01). The EF50 returned to the pre-morphine level at 90 min after injection. These results indicate that morphine produced a moderate antihyperalgesic effect in the tendon injury model. There was also a significant increase in EF50s on the equivalent contralateral site after injection of 4 mg/kg (p < 0.05) and 8 mg/kg (p < 0.01) morphine, confirming the analgesic effect of morphine.


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)

Effects of morphine and duloxetine on EF50s of rats at 8 weeks after ligation of the TASM. The EF50s were below 1 g prior to administration of drugs, indicating the presence of mechanical allodynia. a. Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). Morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). b. Duloxetine was injected i.p. at 0.4, 4, 10 and 20 mg/kg (1 ml/kg, n = 5 per dose). Administration of duloxetine produced significant and dose-dependent increases in EF50s tested at 60 min after injection (ANOVA, P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Effects of morphine and duloxetine on EF50s of rats at 8 weeks after ligation of the TASM. The EF50s were below 1 g prior to administration of drugs, indicating the presence of mechanical allodynia. a. Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). Morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). b. Duloxetine was injected i.p. at 0.4, 4, 10 and 20 mg/kg (1 ml/kg, n = 5 per dose). Administration of duloxetine produced significant and dose-dependent increases in EF50s tested at 60 min after injection (ANOVA, P < 0.01).
Mentions: We finally verified the sensitivity of the TASM injury model to morphine and duloxetine, the two agents that are clinically used as analgesics and commonly used in preclinical studies [28,29]. The effects of morphine and duloxetine were evaluated in rats at 8 weeks after ligation of the TASM when persistent mechanical hyperalgesia/allodynia had developed (Fig. 2a). Morphine was injected s.c. at 0.4, 4 and 8 mg/kg (1 ml/kg, n = 5 per dose). As shown in Fig. 7a, subcutaneous administration of morphine produced significant and dose-dependent increases in EF50s tested at 45 min after injection (ANOVA, P < 0.01). Compared to pre-morphine EF50 of 0.45 g (95% confidence interval: 0.38-0.53 g), 4 mg/kg of morphine elevated EF50 to 20.9 g (13.1-33.4 g) (p < 0.01). The EF50 returned to the pre-morphine level at 90 min after injection. These results indicate that morphine produced a moderate antihyperalgesic effect in the tendon injury model. There was also a significant increase in EF50s on the equivalent contralateral site after injection of 4 mg/kg (p < 0.05) and 8 mg/kg (p < 0.01) morphine, confirming the analgesic effect of morphine.

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