Rat dorsal horn neurons primed by stress develop a long-lasting manifest sensitization after a short-lasting nociceptive low back input

BACKGROUND: A single injection of nerve growth factor (NGF) into a low back muscle induces a latent sensitization of rat dorsal horn neurons (DHNs) that primes for a manifest sensitization by a subsequent second NGF injection. Repeated restraint stress also causes a latent DHN sensitization. OBJECTIVE: In this study, we investigated whether repeated restraint stress followed by a single NGF injection causes a manifest sensitization of DHNs. METHODS: Rats were stressed repeatedly in a narrow plastic restrainer (1 hour on 12 consecutive days). Control animals were handled but not restrained. Two days after stress paradigm, behavioral tests and electrophysiological in vivo recordings from single DHNs were performed. Mild nociceptive low back input was induced by a single NGF injection into the lumbar multifidus muscle just before the recording started. RESULTS: Restraint stress slightly lowered the low back pressure pain threshold (Cohen d = 0.83). Subsequent NGF injection increased the proportion of neurons responsive to deep low back input (control + NGF: 14%, stress + NGF: 39%; P = 0.041), mostly for neurons with input from outside the low back (7% vs 26%; P = 0.081). There was an increased proportion of neurons with resting activity (28% vs 55%; P = 0.039), especially in neurons having deep input (0% vs 26%; P = 0.004). CONCLUSIONS: The results indicate that stress followed by a short-lasting nociceptive input causes manifest sensitization of DHNs to deep input, mainly from tissue outside the low back associated with an increased resting activity. These findings on neuronal mechanisms in our rodent model suggest how stress might predispose to radiating pain in patients.