Dopamine receptor D2, but not D1, mediates descending dopaminergic pathway–produced analgesic effect in a trigeminal neuropathic pain mouse model. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Liu, Sufang; Tang, Yuanyuan; Shu, Hui; Tatum, Delton; Bai, Qian; Crawford, Joshua; Xing, Ying; Lobo, Mary Kay; Bellinger, Larry; Kramer, Phillip; Tao, Feng
• Is Part Of: Pain. Volume 160:Issue 2(2019)
• Publication Date: 2019-02
• Subjects: Dopamine -- Neuropathic pain -- Descending modulation -- Optogenetics -- Chemogenetics; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001414
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Neuropathic pain represents a challenge to clinicians because it is resistant to commonly prescribed analgesics due to its largely unknown mechanisms. Here, we investigated a descending dopaminergic pathway–mediated modulation of trigeminal neuropathic pain. We performed chronic constriction injury of the infraorbital nerve from the maxillary branch of trigeminal nerve to induce trigeminal neuropathic pain in mice. Our retrograde tracing showed that the descending dopaminergic projection from hypothalamic A11 nucleus to spinal trigeminal nucleus caudalis is bilateral. Optogenetic/chemogenetic manipulation of dopamine receptors D1 and D2 in the spinal trigeminal nucleus caudalis produced opposite effects on the nerve injury–induced trigeminal neuropathic pain. Specific excitation of dopaminergic neurons in the A11 nucleus attenuated the trigeminal neuropathic pain through the activation of D2 receptors in the spinal trigeminal nucleus caudalis. Conversely, specific ablation of the A11 dopaminergic neurons exacerbated such pain. Our results suggest that the descending A11−spinal trigeminal nucleus caudalis dopaminergic projection is critical for the modulation of trigeminal neuropathic pain and could be manipulated to treat such pain. Abstract : Supplemental Digital Content is Available in the Text.The descending A11−spinal trigeminal nucleus caudalis dopaminergic pathway–produced analgesic effect on trigeminal neuropathic pain is mediated by dopamine receptor D2, but not D1.