Central Sensitization Induced in Trigeminal and Upper Cervical Dorsal Horn Neurons by Noxious Stimulation of Deep Cervical Paraspinal Tissues in Rats With Minimal Surgical Trauma

ObjectiveThis study investigated if central sensitization is induced in the trigeminal subnucleus caudalis (also termed the medullary dorsal horn) and C1 and C2 dorsal horns by noxious stimulation of deep upper cervical paraspinal tissues in a preparation relatively free of surgical trauma.MethodsAdult male Sprague-Dawley rats (275-450 g) were anesthetized intraperitoneally. Animals were then placed in a stereotaxic frame; a small cutaneous incision was made 3 to 4 mm near the bregma in the midline, and an opening into the skull was prepared by a 1/32-inch drill, 1 mm to the left from the midline. An epoxylite-coated tungsten microelectrode was introduced at an 18° angle to enter this small opening on the skull and was then carefully advanced about 16 mm through cortex, cerebellum, and brainstem to reach subsequently histologically confirmed sites in the Vc and upper cervical (C1 and C2) dorsal horn region. Thirty-three, 27, and 15 neurons recorded in medullary, C1, and C2 dorsal horns, respectively, of chloralose/urethane-anesthetized rats were activated by noxious stimulation of mechanoreceptive fields involving V1, V2, and/or V3 trigeminal nerve territories. The inflammatory irritant mustard oil was injected into the deep paraspinal tissues at the level of the left C1-C2 joint. Pre and postinjection receptive field (RF) sizes were mapped by nonnoxious mechanical stimuli and noxious mechanical and heat stimuli.ResultsA 30- to 50-minute increase (mean, 165% ± 38.1%) in RF size postinjection for 62% of neurons tested was demonstrated, suggesting central sensitization; for most (>70%) neurons, the RF expanded caudally into cervically innervated tissues.ConclusionsThese findings provide the first documentation that deep cervical nociceptive inputs can induce central sensitization in medullary and C1/C2 dorsal horns and suggest that these effects may reflect mechanisms contributing to deep cervical pain and its referral.