Figure 2.

Electrophysiological alterations of primary sensory neurons in oral cancer. (A) The tumor microenvironment (TME) is innervated by both high-threshold mechanoreceptors (slow CHTMRs or fast AHTMRs; nociceptors) and low-threshold mechanoreceptors (LTMRs; tactile afferents). Hypothetical mechanistic links between primary afferent neuron electrophysiological properties and pain phenotype: LTMR desensitization (an increase in mechanical thresholds) and complete loss of mechanosensitivity in LTMR subpopulations could explain partial or complete loss in touch sensitivities in some patients. HTMR sensitization (a decrease in mechanical thresholds) could explain for mechanical pain. Spontaneous firing in nociceptors could explain spontaneous pain experienced by patients. (B) Graphical representation of the shift in pain thresholds during pain states and the observed peripheral effects. N_o, nociceptive threshold; T_o, tactile threshold. LTMR thresholds are increased and HTMR thresholds are decreased in mouse sciatic nerves with PNI. A hyperalgesic state to mechanical stimulation is hypothetically an outcome of an increased excitatory input resulting from HTMR sensitization and a decreased inhibitory input resulting from LTMR desensitization to the pain circuitry.