Abstract
Neuropathic pain refers to pain caused by lesions or diseases of the somatosensory nervous system that is characteristically different from nociceptive pain. Moreover, neuropathic pain occurs in the maxillofacial region due to various factors and is treated using tricyclic antidepressants and nerve block therapy; however, some cases do not fully recover. Netrin is a secreted protein crucially involved in neural circuit formation during development, including cell migration, cell death, neurite formation, and synapse formation. Recent studies show Netrin-4 expressed in the dorsal horn of the spinal cord is associated with chronic pain. Here we found involvement of Netrin-4 in neuropathic pain in the maxillofacial region. Netrin-4, along with one of its receptors, Unc5B, are expressed in the caudal subnucleus of the trigeminal spinal tract nucleus. Inhibition of its binding by anti-Netrin-4 antibodies not only shows a behavioral analgesic effect but also neuronal activity suppression. There was increased Netrin-4 expression at 14 days after infraorbital nerve injury. Our findings suggest that Netrin-4 induced by peripheral nerve injury causes neuropathic pain via Unc5B.
Highlights
Neuropathic pain is defined as “pain caused by a lesion or disease of the somatosensory system” by the International Association for the Study of Pain [1] and is characteristically different from nociceptive pain
We previously reported that Netrin-4 delivered by dorsal horn interneurons was involved in inflammatory and neuropathic pain and that inhibition of Netrin-4 binding to Unc5B suppressed postnerve-injury neuropathic pain [16]
Netrin-4 is associated with allodynia in a trigeminal neuropathic pain nerve injury [16], exerted an analgesic effect on neuropathic pain caused by infraorbital nerve injury
Summary
Neuropathic pain is defined as “pain caused by a lesion or disease of the somatosensory system” by the International Association for the Study of Pain [1] and is characteristically different from nociceptive pain. It involves spontaneous sensations (persistent or intermittent) and stimulation-induced pain (allodynia and hyperalgesia) in areas coinciding with the impaired innervation area, as well as various sensations induced by nerve damage. There is a characteristic of converging abnormalities [2] It might involve the trigeminal nerve region as a result of various factors, including surgery-induced trauma, tumors, neurodegenerative diseases, etc. During dental treatments, nerves are inevitably mechanically cut during teeth extraction; there could be accidental damage to the lingual nerve
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