Pain chronification and chronic pain impair a defensive behavior, but not the ability of acute pain to facilitate it, through the activation of an endogenous analgesia circuit.

Abstract

The endogenous ability to decrease pain perception during life-threatening situations is crucial to the prevention of recuperative behaviors and to leave the subject free to engage in appropriated defensive responses. We have previously shown that acute pain activates the ascending nociceptive control—an endogenous analgesia circuit dependent on opioid mechanisms within nucleus accumbens—to facilitate the tonic immobility response, an innate defensive behavior. Now we asked whether chronic pain and pain chronification impairs either the tonic immobility response or the ability of acute pain to facilitate it by activating the ascending nociceptive control. We found a significant decrease in the duration of the tonic immobility response in rats during the induction and maintenance phases of the persistent mechanical hyperalgesia. This finding suggests that chronic pain and its development impair defensive responses. However, during the induction and maintenance phases of persistent hyperalgesia, the ascending nociceptive control activation, by a forepaw capsaicin injection, increased the tonic immobility response, an effect prevented by the blockade of μ-opioid receptors within nucleus accumbens. This finding suggests that pain chronification and chronic pain do not prevent the ability of acute pain to facilitate the defensive behavior of tonic immobility by activating the ascending nociceptive control. Therefore, although chronic pain states decrease the ability to engage in a defensive behavior, they may not prevent the expression of defensive behaviors during life-threatening situations accompanied by acute pain. The biological purpose of such a mechanism may be to increase the chances of survival of a wounded subject exposed to acute pain in a novel life-threatening situation.

Freeze-like responses to pain in humans and its modulation by social context

“…In addition, freezing responses in patients with chronic pain should be compared to pain-free controls to investigate possible differences in defensive responding. There is some evidence for maladaptive freezing responses in other psychopathologies such as PTSD ( Niermann, Figner & Roelofs, 2017 ) and in rats with chronic pain ( Lamana et al, 2018 ), but research in humans is absent. It is well established that patients move differently when they are in pain ( Hodges & Tucker, 2011 ) and even the anticipation of pain changes movement ( Karos et al, 2017 ).…”

Peer Review #1 of "Freeze-like responses to pain in humans and its modulation by social context (v0.2)"

“…In addition, freezing responses in patients with chronic pain should be compared to pain-free controls to investigate possible differences in defensive responding. There is some evidence for maladaptive freezing responses in other psychopathologies such as PTSD [53] and in rats with chronic pain [44], but research in humans is absent. It is well established that patients move differently when they are in pain [27] and even the anticipation of pain changes movement [32].…”

Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions

“…The transition from acute to chronic pain involves not only the neural network but a series of mediators such as non-neuronal (microglia, astrocytes, and Schwann cells) and inflammatory (neutrophils, macrophages) cells along with various cytokines, vasoactive mediators, chemokines, and their respective receptors [ 16 ]. While detrimental to physical and emotional well-being, chronic pain conditions can also alter the defensive capacities of an individual [ 17 ]. This is mainly because chronic pain goes hand in hand with inflammation.…”