Central high mobility group box-1 induces mechanical hypersensitivity with spinal microglial activation in a mouse model of hemi-Parkinson's disease.
Biomed Pharmacother
; 145: 112479, 2022 Jan.
Article
en En
| MEDLINE
| ID: mdl-34915668
ABSTRACT
Parkinson's disease (PD) patients often complain of pain, but this problem has been neglected and is poorly understood. High mobility group box-1 (HMGB1), an alarmin/damage-associated molecular patterns protein, is increased in the cerebrospinal fluid in PD patients. However, little is known of the relationship between HMGB1 and pain associated with PD. Here, we investigated the role of central HMGB1 in the regulation of nociceptive hypersensitivity in a mouse model of PD. Male ddY mice were microinjected unilaterally with 6-hydroxydopamine (6OHDA) into the striatum. These hemi-PD mice were treated with anti-HMGB1 neutralizing antibody (nAb; 10 µg in 10 µL) by intranasal (i.n.) administration. The mechanical hypersensitivity of the hind paws was evaluated with the von Frey test. Spinal microglial activity was analyzed by immunostaining for ionized calcium-binding adapter molecule 1. The 6OHDA-administered mice displayed unilateral loss of dopamine neurons in the substantia nigra and mechanical hypersensitivity in both hind paws. Moreover, spinal microglia were activated in these hemi-PD mice. Twenty-eight days after the 6OHDA injections, repeated i.n., but not systemic, treatment with anti-HMGB1 nAb inhibited the bilateral mechanical hypersensitivity and spinal microglial activation. However, the anti-HMGB1 nAb did not ameliorate the dopamine neuron loss. Moreover, intracerebroventricular injection with recombinant HMGB1 induced mechanical hypersensitivity. These findings indicate that HMGB1 is involved in the maintenance of nociceptive symptoms in hemi-PD mice via spinal microglial activation. Therefore, central HMGB1 may have potential as a therapeutic target for pain associated with PD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Enfermedad de Parkinson
/
Médula Espinal
/
Microglía
/
Proteína HMGB1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón