Pathophysiology of the constant burning, tingling element of neuropathic pain: A new hypothesis

Neuropathic pain (NPP) presents itself with at least one of the following elements: constant, intermittent and evoked pain. The pathophysiology of NPP is still controversial, in especial of its constant element, the focus of this study. Many hypotheses have been proposed in an attempt to explain it, but none of them seems to account for the various aspects of the constant element of NPP. Under the phylogenetic perspective, it is postulated, the pain may be classified into two categories: paleopain, present in inferior animals, poorly localized, transmitted by the medial pain system pathways, and neopain, conducted by the lateral pain system pathways, very well localized, described in terms suggestive of tissue damage and present in superior animals. We believe that, in humans, under physiological circumstances, the expression of the paleopain was completely abolished. It is proposed that it is due to the tonic inhibition of the medial thalamus by the ventral posterior (VP) nucleus of the thalamus, via a circuit that the authors described and named prosencephalomesencephalic modulatory circuit (PMMC). Two pathways are suggested as activators of the PMMC: the neospinothalamic/neotrigeminothalamic and ventral spinothalamic tracts. The interruption of this circuit or of its activators, at any point, would lead to the release of the medial thalamus from the inhibitory influences of VP, allowing the manifestation of the paleopain. It is postulated that the constant burning, tingling element of NPP is nothing more than the clinical expression of the paleopain. Evidence to support this hypothesis is provided. As a direct consequence of the presented hypothesis, the substantia nigra pars reticulata is proposed as a new target of deep brain stimulation for the treatment of the constant burning, tingling element of NPP.