Figure 8.

Induction of the mirror-image pain and contralateral hypersensitivity. Schematic illustrating how disinhibition of the decussating pathways can cause induction of the mirror-image pain. Based on our data, three inhibitory pathways are considered. Pathway 1, the contralateral Aβδ-afferent-driven presynaptic inhibition of the contralateral C-fiber input (Fig. 4A1,A2). Pathway 2, tonic network inhibition of the contralateral input (Fig. 4B1). The tonic inhibition of the C-fiber directly supplying Lamina I neuron is not indicated. Pathway 3, the contralateral Aβδ-afferent-driven presynaptic inhibition of the ipsilateral input (Fig. 6B,C). Disinhibition of pathways 1 and 2 will allow the ongoing afferent barrage in the injured nerve (red) to reach a Lamina I PN on the uninjured side (blue). Its excitation by the contralateral afferent barrage will result in a perception of pain as arising from the ipsilateral receptive field (RF) even if there is no activity in the ipsilateral afferents (Mirror-Image Pain). Disinhibition of pathway 3 will increase the ipsilateral afferent drive reaching a PN on uninjured side after stimulation of its ipsilateral receptive field. Note that the ipsilateral input can be affected even in the neuron that does not receive contralateral supply. This can reduce the noxious threshold for the ipsilateral receptive field and increase the nociceptive afferent discharge reaching the PN, thereby contributing to development of allodynia and hyperalgesia on the uninjured side (Contralateral Hypersensitivity). The hyperalgesia can further be augmented by disinhibition of pathways 1 and 2 that will open a gate allowing injured afferent barrage to reach the contralateral PN. Inhibitory interneurons are shown in green, an excitatory neuron in orange.