Nociceptive modulation; Pain modulation; Endogenous analgesia system; Descending pain modulation
Descending pain modulation encompasses pathways that descend from the forebrain and brainstem to the spinal cord and trigeminal sensory complex to modify incoming somatosensory information so that the perception of and reactions to somatosensory stimuli are altered, resulting in either less or more pain.
That mammalian sensory systems do not record the world faithfully is so obvious as to border on the cliché. Visual, auditory and somatosensory illusions are clear evidence that what we perceive differs from what exists externally. In the case of pain, a function absolutely critical to survival, it is remarkable that a given stimulus (or lack of stimulus) does not reliably evoke a predictable sensation. Under some circumstances, sensory perception is dominated by ascending nociceptive pathways as one may expect; however, there are a myriad of circumstances when sensory perception follows primarily from the effects of descending sensory modulation. Descending pain modulation can make one perceive and react to an innocuous stimulus as though it were painful. Holding a cold can of beer – the same can that felt ever so good on a hot summer day – in sub-freezing temperatures is unpleasant and even painful and chances are, you will drop the can. Pathological examples of “false positive” pains abound in the realm of the spontaneous pain that accompanies a number of neuropathic conditions, at least some of which depend on descending modulation for their initiation and maintenance. Examples of “false negatives” – noxious stimuli that fail to elicit a sensation of pain – also abound. One of the best articulated examples of this is David Livingstone’s feeling of “a sort of dreaminess, in which there was no sense of pain,” after being mauled by a lion (who Livingstone had just shot and injured), to the extent that his bone was splintered and skin permanently scarred . These two examples represent two extremes on a continuum of sensitivity to cutaneous stimulation that ranges from insensitive (Livingstone) to inappropriately sensitive (holding cold beer on a freezing day).
The disconnect between the somatosensory worlds, outside and perceived, does not result from errors in the faithful, labeled-line, ascending sensory pathways, but rather from modulation of these same systems. Pain modulation happens at every level of the sensory pathway: at the peripheral terminal, the nerve, dorsal horn and on up the neuraxis. Touching one’s skin before and after basking in the sun for hours elicits very different sensations because a number of inflammatory chemicals modulate the sensitivity of peripheral afferents. Yet, the exquisite sensitivity to touch resulting from a sunburn is not very different under different contexts. In order for modulation to be context-specific, the modulatory signal must arise from regions rostral to the spinal cord where information about context is available. Thus modulatory signals that alter nociceptive processing in accordance with context or meaning descend from the brainstem and forebrain. While some modulation ascends to modify thalamo-cortical processing of sensory input, it is clear that most pain modulation descends to the dorsal horn where it modifies the discharge of dorsal horn neurons that respond to nociceptor activation. In this way the dominant mode of pain modulation is to modify transmission at the earliest central synapses in the dorsal horn.
Raphe magnus can either inhibit or facilitate nociceptive transmission. Under normal circumstances and in healthy animals, the inhibitory effects predominate. However, descending facilitation from raphe magnus is a necessary component for certain neuropathic pain syndromes . It is interesting to note that under these same circumstances, descending inhibitory influences from the medullary raphe also appear to be enhanced, perhaps in an attempt, albeit unsuccessful, to suppress the on-going neuropathic pain signal .
The medullary raphe suppresses low threshold as well as nociceptive responses in dorsal horn neurons . Raphe magnus stimulation also modulates thermoreceptive responses in the superficial dorsal horn . Thus, descending modulation from raphe magnus likely targets a variety of sensory inputs rather than only nociceptive ones.
Medullary raphe and ventral reticular neurons project heavily to the intermediate gray, including the thoracic and sacral intermedio-lateral and medial cell columns and to the central canal region. These cells also project oligosynaptically to sympathetically- and parasympathetically-innervated tissues as well as to some somatomotor muscles, all of which are involved in maintaining homeostasis . Activation of medullary raphe neurons results in a number of homeostatic adjustments, evidence for a role beyond one of simple sensory modulation.