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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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Effect of local anesthesia on mechanical allodynia and hyperalgesia after TASM ligation. To verify allodynia/hyperalgesia related to tendon injury, local anesthesia was induced in the intraoral site around the TASM or the overlying skin ipsilaterally by lidocaine (4%, 0.05-0.2 ml) in rats receiving tendon ligation and having developed allodynia/hyperalgesia. Compared to saline-treated rats (Saline-Intraoral, n = 5), allodynia/hyperalgesia was significantly attenuated when lidocaine was infiltrated into the TASM site (Lido-Intraoral, n = 5) at 30 min after lidocaine (***, p < 0.001, vs. saline). Local anesthesia of the skin overlying TASM (Lido-Cutaneous, n = 5) did not affect hyperalgesia. Note that some symbols are slightly shifted horizontally for clarity. Error bars represent 95% confidence intervals.
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Figure 3: Effect of local anesthesia on mechanical allodynia and hyperalgesia after TASM ligation. To verify allodynia/hyperalgesia related to tendon injury, local anesthesia was induced in the intraoral site around the TASM or the overlying skin ipsilaterally by lidocaine (4%, 0.05-0.2 ml) in rats receiving tendon ligation and having developed allodynia/hyperalgesia. Compared to saline-treated rats (Saline-Intraoral, n = 5), allodynia/hyperalgesia was significantly attenuated when lidocaine was infiltrated into the TASM site (Lido-Intraoral, n = 5) at 30 min after lidocaine (***, p < 0.001, vs. saline). Local anesthesia of the skin overlying TASM (Lido-Cutaneous, n = 5) did not affect hyperalgesia. Note that some symbols are slightly shifted horizontally for clarity. Error bars represent 95% confidence intervals.

Mentions: We assessed the mechanical sensitivity of the tendon through probing the overlying skin. Although deep tissue primary afferents are activated by this mechanical pressure, a problem with this approach is that cutaneous afferents are also stimulated and may contribute to the pain-pressure threshold [22]. To verify deep origin of hyperalgesia after the tendon injury, we induced anesthesia by infiltrating the local anesthetic lidocaine (4%, 0.05-0.2 ml) into tissues surrounding the TASM or the overlying skin in rats that had developed hyperalgesia after tendon ligation. The hyperalgesia was largely attenuated, as shown by a significantly increase in EF50 (p < 0.001, n = 5), when the TASM was anesthetized as compared to saline-treated rats (Fig. 3). The effect of local anesthesia started to wear off after 60 min (Fig. 3). In contrast, the tendon injury-induced hyperalgesia was not affected when the overlying skin testing site was anesthetized (n = 5) (Fig. 3). Thus, a reduction of EF50 at the testing site in tendon-ligated rats reflects tenderness and increased sensitivity of deep tissue. This is consistent with previous results that masseter hyperalgesia was detectable when the overlying skin site was anesthetized [23].


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)

Effect of local anesthesia on mechanical allodynia and hyperalgesia after TASM ligation. To verify allodynia/hyperalgesia related to tendon injury, local anesthesia was induced in the intraoral site around the TASM or the overlying skin ipsilaterally by lidocaine (4%, 0.05-0.2 ml) in rats receiving tendon ligation and having developed allodynia/hyperalgesia. Compared to saline-treated rats (Saline-Intraoral, n = 5), allodynia/hyperalgesia was significantly attenuated when lidocaine was infiltrated into the TASM site (Lido-Intraoral, n = 5) at 30 min after lidocaine (***, p < 0.001, vs. saline). Local anesthesia of the skin overlying TASM (Lido-Cutaneous, n = 5) did not affect hyperalgesia. Note that some symbols are slightly shifted horizontally for clarity. Error bars represent 95% confidence intervals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effect of local anesthesia on mechanical allodynia and hyperalgesia after TASM ligation. To verify allodynia/hyperalgesia related to tendon injury, local anesthesia was induced in the intraoral site around the TASM or the overlying skin ipsilaterally by lidocaine (4%, 0.05-0.2 ml) in rats receiving tendon ligation and having developed allodynia/hyperalgesia. Compared to saline-treated rats (Saline-Intraoral, n = 5), allodynia/hyperalgesia was significantly attenuated when lidocaine was infiltrated into the TASM site (Lido-Intraoral, n = 5) at 30 min after lidocaine (***, p < 0.001, vs. saline). Local anesthesia of the skin overlying TASM (Lido-Cutaneous, n = 5) did not affect hyperalgesia. Note that some symbols are slightly shifted horizontally for clarity. Error bars represent 95% confidence intervals.
Mentions: We assessed the mechanical sensitivity of the tendon through probing the overlying skin. Although deep tissue primary afferents are activated by this mechanical pressure, a problem with this approach is that cutaneous afferents are also stimulated and may contribute to the pain-pressure threshold [22]. To verify deep origin of hyperalgesia after the tendon injury, we induced anesthesia by infiltrating the local anesthetic lidocaine (4%, 0.05-0.2 ml) into tissues surrounding the TASM or the overlying skin in rats that had developed hyperalgesia after tendon ligation. The hyperalgesia was largely attenuated, as shown by a significantly increase in EF50 (p < 0.001, n = 5), when the TASM was anesthetized as compared to saline-treated rats (Fig. 3). The effect of local anesthesia started to wear off after 60 min (Fig. 3). In contrast, the tendon injury-induced hyperalgesia was not affected when the overlying skin testing site was anesthetized (n = 5) (Fig. 3). Thus, a reduction of EF50 at the testing site in tendon-ligated rats reflects tenderness and increased sensitivity of deep tissue. This is consistent with previous results that masseter hyperalgesia was detectable when the overlying skin site was anesthetized [23].

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