Effect of a Novel, Orally Active Matrix Metalloproteinase-2 and -9 Inhibitor in Spinal and Trigeminal Rat Models of Neuropathic Pain.
J Oral Facial Pain Headache
; 29(3): 286-96, 2015.
Article
en En
| MEDLINE
| ID: mdl-26244437
ABSTRACT
AIMS:
To study the effects of a novel matrix metalloproteinase-2 (MMP-2) and MMP-9 inhibitor, AQU-118, on mechanical allodynia in the spinal nerve ligation (SNL) model of neuropathic pain and the chronic constriction injury of the infraorbital nerve (CCI-IoN) model of neuropathic orofacial pain.METHODS:
Five groups of SNL rats were given daily oral doses of AQU-118 (5, 10, 20 mg/kg), gabapentin (100 mg/kg), or vehicle (0.5% methylcellulose) and then paw withdrawal threshold was measured with von Frey filaments (VF). Three groups of CCI-IoN rats were given daily oral doses of either AQU-118 (40 mg/kg), gabapentin (100 mg/kg), or vehicle (0.5% methylcellulose) and then mechanical allodynia was measured with facial VF and non-reflex-based orofacial stimulation test (OFST) assay. Naïve rats were also tested for the effect of AQU-118 (40 mg/kg) on basal sensitivity to mechanical stimulation/locomotive activity.RESULTS:
Mechanical allodynia in SNL rats was attenuated by gabapentin (100 mg/kg) and AQU-118 (in a dose-dependent manner). Mechanical allodynia in CCI-IoN rats was also attenuated (in an equipotent manner) by both AQU-118 (40 mg/ kg) and gabapentin (100 mg/kg) as measured by both facial VF and OFST assay. Upon cessation of either AQU-118 or gabapentin, VF-related responses in both models and OFST assay times reverted to levels observed in vehicle-treated rats. No statistically significant change was observed in locomotive activity/paw withdrawal threshold by AQU-118 (40 mg/kg) in naïve rats.CONCLUSION:
The results demonstrated that oral AQU-118 attenuates mechanical allodynia in both neuropathic pain models and with efficacies that mirror gabapentin at the 40 mg/kg dose used in the CCI-IoN model but without effect on basal sensitivity to mechanical stimulation/locomotive activity. These findings support a possible role for MMP-2/-9 in the etiology of neuropathic pain and also suggest that inhibition strategies represent a viable treatment option.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propionatos
/
Tiofenos
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Ácidos Ciclohexanocarboxílicos
/
Inhibidores de la Metaloproteinasa de la Matriz
/
Ácido gamma-Aminobutírico
/
Aminas
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Hiperalgesia
/
Indoles
/
Neuralgia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Oral Facial Pain Headache
Año:
2015
Tipo del documento:
Article