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Peripheral oxytocin restores light touch and nociceptor sensory afferents towards normal after nerve injury

Boada, M. Danilo; Gutierrez, Silvia; Eisenach, James C.*

doi: 10.1097/j.pain.0000000000001495
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Oxytocin reduces primary sensory afferent excitability and produces analgesia in part through a peripheral mechanism, yet its actions on physiologically characterized, mechanically sensitive afferents in normal and neuropathic conditions are unknown. We recorded intracellularly from L4 dorsal root ganglion neurons characterized as low-threshold mechanoreceptors (LTMRs) or high-threshold mechanoreceptors (HTMRs) in female rats 1 week after L5 partial spinal nerve injury or sham control (n = 24 rats/group) before, during, and after ganglionic perfusion with oxytocin, 1 nM. Nerve injury desensitized and hyperpolarized LTMRs (membrane potential [Em] was −63 ± 1.8 mV in sham vs −76 ± 1.4 mV in nerve injury; P < 0.001), and sensitized HTMRs without affecting Em. In nerve-injured rats, oxytocin depolarized LTMRs towards normal (Em = −69 ± 1.9 mV) and, in 6 of 21 neurons, resulted in spontaneous action potentials. By contrast, oxytocin hyperpolarized HTMRs (Em = −68 ± 2.7 mV before vs −80 ± 3.2 mV during oxytocin exposure; P < 0.01). These effects were reversed after removal of oxytocin, and oxytocin had minimal effects in neurons from sham surgery animals. Sensory afferent neurons immunopositive for the vasopressin 1a receptor were larger (34 ± 6.3 μm, range 16-57 μm) than immunonegative neurons (26 ± 3.4 μm, range 15-43 μm; P < 0.005). These data replicate findings that neuropathic injury desensitizes LTMRs while sensitizing HTMRs and show rapid and divergent oxytocin effects on these afferent subtypes towards normal, potentially rebalancing input to the central nervous system. Vasopressin 1a receptors are present on medium to large diameter afferent neurons and could represent oxytocin's target.

Oxytocin's analgesic mechanisms are uncertain. In nerve-injured animals, acute oxytocin exposure to sensory afferent neurons hyperpolarizes sensitized mechanical nociceptors and depolarizes desensitized tactile afferents, returning peripheral input towards normal.

Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, United States

Corresponding author. Address: Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC 27157-1009, United States. Tel.: (336)-716-4182; fax: (336) 716-0288. E-mail address: eisenach@gmail.com (J.C. Eisenach).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received September 13, 2018

Received in revised form December 12, 2018

Accepted December 26, 2018

© 2019 International Association for the Study of Pain
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