Sustained morphine exposure alters spinal NMDA receptor and astrocyte expression and exacerbates chronic pain behavior in female rats.
Pain Rep
; 9(2): e1145, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38482044
ABSTRACT
Introduction:
Sustained opioid use has long-term negative impacts on future pain experience, particularly in women. This study aimed to investigate the underlying spinal neurobiology of this clinical observation in an experimental model of joint pain.Objectives:
In this study, we tested the hypothesis that sustained opioid treatment exacerbates chronic pain responses and alters spinal cord dorsal horn astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors in female rats.Methods:
Subcutaneous morphine (3 mg/kg) or saline was administered twice daily for 1 week before inducing a model of joint knee pain (intra-articular injection of 2 mg of monosodium iodoacetate [MIA]) in adult female Sprague-Dawley rats, with pain-free controls receiving 50 µL of saline. Pain behavior (weight-bearing and mechanical paw withdrawal thresholds) was measured at baseline and at intervals thereafter. Twice-daily morphine/saline treatment was continued for up to 3 weeks after intra-articular injections, and spinal cord tissue was collected for Western blot analyses.Results:
Area under the curve analysis of weight-bearing asymmetry confirmed a significant exacerbation of pain behavior in the morphine/MIA group, compared with the saline/MIA group (F(3,18) = 46.3, P < 0.0001), despite comparable joint damage in both groups. Sustained morphine treatment was associated with significant elevations in dorsal horn expression of astrocytic glial fibrillary acidic protein (27 ± 5% increase) and neuronal GluN2B (80 ± 30% increase), but not microglial IBA1, irrespective of the model of joint pain.Conclusion:
These data suggest that sustained morphine treatment in female rats drives spinal cord plasticity, including spinal astrogliosis and the expression of GluN2B-containing N-methyl-d-aspartate receptors, priming the dorsal horn to incoming sensory inputs and producing exacerbated pain responses.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Pain Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Reino Unido