Descending facilitatory pain pathways mediate ongoing pain and tactile hypersensitivity in a rat model of trigeminal neuropathic pain

The Chronic Constriction Injury of the Infraorbital Nerve (CCI-ION) is a well-established model to study facial sensory changes related to trigeminal neuropathic pain. CCI-ION induces heat hypersensitivity that resolves within 2-3 weeks and a delayed mechanical hypersensitivity that emerges during the second week post-injury. The role of descending facilitatory pain pathways from the rostro ventromedial medulla (RVM) in mediating the heat and tactile hypersensitivity was examined. CCI-ION induced heat hypersensitivity observed 5days post-surgery was reversed by systemic, but not RVM lidocaine. CCI-ION-induced tactile hypersensitivity observed 15days post-surgery was reversed by systemic lidocaine and attenuated by RVM lidocaine. CCI-ION-induced spontaneous pain was determined using conditioned place preference (CPP) to pain relief at each time-point. At day 5 post-CCI-ION, neither systemic nor RVM lidocaine induced CPP. However, at 15days post-CCI-ION, CPP was observed to the chamber paired with RVM lidocaine, but not systemic lidocaine. These data indicate that CCI-ION induced heat hypersensitivity is not dependent on descending facilitatory pain pathways 5-days post-injury whereas descending facilitatory pain pathways mediate tactile allodynia and spontaneous pain 15days post-CCI-ION. This suggests that CCI-ION induces early peripheral sensitization followed by development of central sensitization that mediates spontaneous pain and contributes to mechanical hypersensitivity.