Peggy Mason
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, IL, USA

https://doi.org/10.36866/pn.65.23

Pain is a perceptual experience that is ascribed to a body part and has a negative effect. Under normal circumstances, the stimuli that elicit pain are tissue-damaging or would cause tissue damage were they to persist: in short, noxious stimuli. Under these same conditions, noxious stimuli elicit a report of pain in verbal humans.

While the gold standard for pain perception will always be verbal report, ontological and phylogenetic continuity are most consistent with the idea that non-verbal humans and animals, at least mammals, experience pain. I will therefore use the terms pain and painful stimulus to refer to what others term nociception and noxious stimulus. A fundamental distinction can be drawn between acute pain – a transient experience – and persistent or chronic pain. Acute pain requires a stimulus to engage nociceptive pathways. In many forms of chronic pain, no stimulus occurs and nociceptive pathways are activated pathologically.

Acute pain is a common experience of varied intensity, location and meaning. Stubbing a toe or being scratched by a loving pet is transiently bothersome but rapidly forgotten. In contrast, breaking a toe or scratching a cornea evokes intense pain and the circumstances surrounding such events are long remembered. The acute pain experience is at turns protective and debilitating. Short-latency motor reactions to superficial pain stimuli, commonly withdrawals, are protective as are the longer latency, affectively motivated escape strategies including flight and freezing. Although freezing may not commonly be thought of as an escape reaction, it is preferred to flight when a rodent faces a predator within close quarters and serves the same function as flight does in more spacious conditions.

Pain can also be arresting, as anyone that has experienced an acute episode of back pain knows. Immobility (an active state with high muscle tone) elicited by extreme pain is clearly to an individual’s disadvantage, rendering her or him vulnerable to predators or potentially injurious situations. One may postulate that while failing to serve an individual’s immediate safety needs, painful stimulus-evoked immobility is necessary to allow healing from an injury. According to this idea, if one moved about with a ruptured disk, the disk would never heal, a reasonable possibility supported by the prevalence of prescribed bed rest for myriad painful conditions. Thus being frozen in pain may be the only long-term solution to injury despite its immediate inconveniences. Finally, it should be noted that prolonged immobility is survivable only by humans and other highly social animals and is likely lethal in less social species.

In addition to evoking either movement or active immobility, painful stimulation can also be ignored. This happens when animals are feeding, voiding, or highly stressed (Baez et al. 2005; Foo & Mason, 2005). For example, a rat that is eating chow will continue eating chow as heat is applied to his hindpaw, typically never responding to the heat stimulus that causes a brisk withdrawal when the rat is not eating. While one may assume that extremely intense noxious stimuli would elicit a reaction under all circumstances, ethical concerns preclude these experiments and therefore only mild to moderate intensity stimuli are used. Allowing for context-specific modulation of noxious input allows for behavioral flexibility.

Furthermore, this flexibility can serve to adjudicate between the needs of an organism. For example, a rat that has had difficulty finding food may continue to eat, notwithstanding intense noxious stimulation. In contrast that same intense noxious stimulation will likely interrupt a rat that has recently fed. Under natural circumstances, food is relatively scarce and the system may be biased toward feeding, resulting in the failure of moderately painful stimuli to interrupt feeding.

Within the category of acute pain, there are significant differences and few similarities between cutaneous and deep pain. A noxious cutaneous stimulus typically leads to active movements away from the offending situation accompanied by multiple signs of sympatho-excitation. The resulting pain perception is well demarcated in time and space and if of sufficient intensity, a long term memory of the event will ensue. In contrast, a noxious deep stimulus does not elicit movement and often is not immediately accompanied by perception, thereby precluding explicit memory formation of the surrounding circumstances. When of sufficient intensity, deep injury can lead to perception, albeit poorly localized in time and space, as well as immobility and sympatho­inhibition.

Several glaring examples of the subtle effects of deep injury have recently been reported. In one such example, a nail gun backfired, sending a nail into the cheek of the young man operating the gun. After receiving treatment for the cutaneous wound in his cheek, the man returned home. Only a week later, after presenting with a toothache, did it become clear that the nail had actually entered the young man’s cranium and was lodged therein (see Fig. 1). Perhaps even more remarkable was the fact that this was the second such case observed at the suburban Denver hospital where the injury was treated. It is telling to contrast the immediate indifference evoked by such a severe deep tissue injury as described above with the inordinate concern and awareness that accompanies a superficial injury such as a paper cut.

In sum, it is clear that cutaneous and deep pain are very different phenomenologically, leading Thomas Lewis, an early pioneer in pain research, to lament that the somatic experiences of deep and superficial pain share a common moniker (Lewis, 1942).

Several differences exist between the neural mechanisms that support acute cutaneous and deep pain.

Afferents carrying information about cutaneous pain belong to a specific class of nociceptors that are activated only by noxious stimuli that would normally elicit pain. Afferents that carry deep pain input are more heterogeneous with some coding pain exclusively, like cutaneous nociceptors, and some that code both pain and non­painful information.

Another difference between cutaneous and deep pain is the role of descending modulation from the brainstem and forebrain. The net effect of descending modulation onto cutaneous nociceptive pathways is a tonic inhibition. In marked contrast, it appears that for visceral nociception, a spino-bulbo­spinal loop is required for expression of the full behavioral and physiological reaction (Cervero et al. 1985; Ness & Gebhart, 1988).

Taking the differences in behaviour and neural circuitry together leads to the Gertrude Stein-esque conclusion that ‘acute pain is not acute pain is not acute pain’. Put more positively, acute pain is heterogeneous, depending on location, intensity, and context.

References

Baez MA, Brink TS & Mason P (2005). Roles for pain modulatory cells during micturition and continence. J Neurosci 25, 384-394.

Cervero F, Lumb BM & Tattersall JE (1985). Supraspinal loops that mediate visceral inputs to thoracic spinal cord neurones in the cat: involvement of descending pathways from raphe and reticular formation. Neurosci Lett 56, 189-194.

Foo H & Mason P (2005). Sensory suppression during feeding. Proc Natl Acad Sci U S A 102, 16865-16869.

Ness TJ & Gebhart GF (1988). Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudaffective reflexes in the rat. Brain Res 450, 153-169.

Lewis T (1942). Pain. The Macmillan Company, New York.