Pain modulation in the spinal cord

Abstract

The sensory inflow from the periphery that triggers innocuous and painful sensations is highly complex, capturing key elements of the nature of any stimulus, its location, intensity, and duration, and converting this to dynamic action potential firing across a wide population of afferents. While sensory afferents are highly specialized to detect these features, their input to the spinal cord also triggers active processing and modulation there which determines its output, to drive the sensory percept experienced and behavioral responses. Focus on such active spinal modulation was arguably first introduced by Melzack and Wall in their Spinal Cord Gate Control theory. This theory has had a profound influence on our understanding of pain, and especially its processing, as well as leading directly to the development of clinical interventions, and its historical importance certainly needs to be fully recognized. However, the enormous progress we are making in the understanding of the function of the somatosensory system, means that it is time to incorporate these newly discovered features into a more complex and accurate model of spinal sensory modulation.

Microglial P2X4 receptors are essential for spinal neurons hyperexcitability and tactile allodynia in male and female neuropathic mice

“…This result appears contradictory to the enhanced mechanical hypersensitivity observed in P2X4KI mice after SNI, but several hypotheses can be proposed. It is possible that C-fibers are not the only fibers conducting nociceptive inputs, and alterations in Aδ fibers 40 or non-nociceptive Aβ fibers 41 could contribute to the observed effects. In addition, we cannot exclude that other projection neurons, such as nociceptive-specific neurons of lamina I, are also altered and contribute to the increased mechanical hypersensitivity observed in P2X4KI mice after SNI.…”

The introduction and current status of the multidimensional model of pain neurobiology

“…The neuroscientific and clinical evidence then available led to the publication of new hypotheses about somesthetic mechanisms generally ( 17 ) and then to the gate control (GC) hypothesis of pain ( 18 ). The historical background of these seminal conceptual contributions has been reviewed previously ( 19 , 20 ). For the present purpose, it is necessary to note that much of our current information was not available at the time of the SS Symposium and that detailed and definitive studies of the neurophysiology of spinothalamic dorsal horn neurons would not be available for several years later ( 21 ).…”

Stem cells and pain

“…, bacteria, parasites, virus) present virulence factors that can activate nociceptor neurons. For a further in-depth understanding of pain mechanisms in varied conditions we recommend the following review articles[ 125 , 174 - 177 ].…”