CB2 receptor deletion on myeloid cells enhanced mechanical allodynia in a mouse model of neuropathic pain

Elisa Nent, Chihiro Nozaki, Anne Caroline Schmöle, David Otte, Andreas Zimmer

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4 Citations (Scopus)

Abstract

Neuropathic pain can develop after nerve injury, leading to a chronic condition with spontaneous pain and hyperalgesia. Pain is typically restricted to the side of the injured nerve, but may occasionally spread to the contralateral side, a condition that is often referred to as mirror-image pain. Mechanisms leading to mirror-image pain are not completely understood, but cannabinoid CB2 receptors have been implicated. In this study, we use genetic mouse models to address the question if CB2 receptors on neurons or on microglia/macrophages are involved. First, we show that a GFP reporter protein under control of the CB2 promoter is induced upon partial sciatic nerve ligation in spinal cord, dorsal root ganglia, and highest in sciatic nerve macrophages, but not in neurons. Mice which lack CB2 receptors specifically on myeloid cells (microglia, macrophages) developed a mirror-image allodynia [treatment F 1,48 = 45.69, p < 0.0001] similar to constitutive CB2 receptor knockout mice [treatment F 1,70 = 92.41, p < 0.0001]. Such a phenotype was not observed after the deletion of CB2 from neurons [treatment F 1,70 = 0.1315, p = 0.7180]. This behavioral pain phenotype was accompanied by an increased staining of microglia in the dorsal horn of the spinal cord, as evidenced by an enhanced Iba 1 expression [CB2KO, p = 0.0175; CB2-LysM, p = 0.0425]. Similarly, myeloid-selective knockouts showed an increased expression of the leptin receptor in the injured ipsilateral sciatic nerve, thus further supporting the notion that leptin signaling contributes to the increased neuropathic pain responses of CB2 receptor knockout mice. We conclude that CB2 receptors on microglia and macrophages, but not on neurons, modulate neuropathic pain responses.

Original languageEnglish
Article number7468
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

ASJC Scopus subject areas

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