Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

Abstract

BackgroundPrevious animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent pain-related behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear.Methodology/Principal FindingsIn the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain.Conclusions/SignificanceThese results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight the importance of treatment of chronic pain at an early stage.

A Brain Signature to Differentiate Acute and Chronic Pain in Rats

“…Rats injected with CFA exhibited pronounced thermal hyperalgesia that developed within 1 day and persisted through 14 days following injection. This observation is similar to that of previous reports on the temporal profile of thermal hyperalgesia in CFA-induced chronic pain model (Wang et al, 2009 ; Li et al, 2012 ). Three-way ANOVA revealed that PWLs were significantly modulated by “group” ( F (1,19) = 5.8, p = 0.03), “time” ( F (5,95) = 7.5, p < 0.0001), “stimulation site” ( F (1,19) = 43.8, p < 0.0001), interactions between two factors (“group” × “stimulation site”: F (1,19) = 41.0, p < 0.0001 ; “time” × “stimulation site”: F (5,95) = 9.5, p < 0.0001; “group” × “time”: marginal significance, F (5,95) = 2.2, p = 0.06), and the interaction between three factors ( F (5,95) = 7.6, p < 0.0001).…”

Inflammatory pain memory facilitates occlusal interference‐induced masticatory muscle hyperalgesia in rats

“…We further showed that this carrageenan‐induced inflammatory pain memory facilitated the occlusal interference‐induced masseter muscle hyperalgesia. Our results were consistent with previous studies, which showed that the later perception of pain is associated with the previous inflammatory stimulation in a model of repeated inflammatory pain in the hind paws (Kayser et al., ; Li et al., ). Our results were also in good agreement with results of the clinical trials, which showed that children who displayed great distress at lumbar punctures experienced aggravated distress during subsequent lumbar punctures (Chen et al., ); their direct experience of pain intensity and their adult behaviour during venipuncture were related to their memories of past procedures (Noel et al., ).…”

Increasing Pain Sensation Eliminates the Inhibitory Effect of Depression on Evoked Pain in Rats

“…A custom-designed Plexiglas chamber (22 × 22 × 30 cm) was used (Li et al, 2012 ). The chamber had holes (3-mm diameter at 3-mm intervals) in the bottom and a speaker on its back wall.…”

“…Stimulus-elicited behaviors (Fan et al, 1995 ; Li et al, 2012 ) were scored as follows: 0, immobility; 1, head turning (shaking or elevating the head); 2, flinching (a small abrupt jerking body movement); 3, withdrawal (retracted of the paw away from the stimulus) or licking (paw retraction flowed by licking of that paw); and 4, body movement (body turning and running). The rats were videotaped throughout the experiment.…”

“…We expected to observe a transition from an inhibitory to facilitatory effect of depression modulation on evoked pain; (2) Using tone-laser conditioning paradigm and formalin-induced conditioned place avoidance (F-CPA) paradigm, we established a relationship between evoked/spontaneous pain and tone/context and examined the avoidance motivation for both conditions in rats subjected to unpredictable chronic mild stress (UCMS). The behavioral reactions induced by conditioned tone could reflect the avoidance motivation of evoked pain (Li et al, 2012 ), and the conditioned place avoidance behavior was used to investigate the response motivated by ongoing pain (Johansen et al, 2001 ; Navratilova and Porreca, 2014 ). We predicted that the amotivation symptom of depression may lead to decreased pain-avoidance motivation, thus contributing to the inhibitory effect of depression on evoked pain; and (3) Given that monoamine neurotransmitters are shared by pain and depression (Han and Pae, 2015 ; Kaufman et al, 2016 ), we hypothesized that alteration of nociceptive sensitivity in the depressive state may be mediated, at least in part, via serotonin (5-HT) receptors.…”