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The method simulating spontaneous pain in patients with nociplastic pain using rats with fibromyalgia-like condition.

ABSTRACT: The method shown in this article simulates spontaneous pain in patients with nociplastic pain using rats; the measurement with this method could be related to better translation of analgesic efficacies of therapeutic compounds between rats and humans. Nociplastic pain occurs in various disorders including fibromyalgia. Because the pain in patients occurs without an external stimulus, we assessed spontaneous pain in rats. The grimace scale, a methodology for rating facial expression, has been used for measuring spontaneous pain in animals. However, the responses in animals have been rather short-lived, and the scale has never been applied to animals exhibiting nociplastic pain. Here, we apply the rat grimace scale (RGS) to the reserpine-induced fibromyalgia-like rat, which induces nociplastic pain. The ratings of the orbital tightening, nose/cheek flattening, and changes in characteristics of ears and whiskers by three raters, who were blinded to the treatment allocated to rats, demonstrated substantial, long-lasting change in facial expression of rats. In this article, reference images for raters, and sample images used for rater training are provided. All raters independently indicated that the RGS score is significantly elevated with this methodology in reserpine-induced fibromyalgia-like rats.•The grimace scale, a method for rating facial expression, is applied to the reserpine-induced fibromyalgia-like rat, which manifests nociplastic pain.•Facial expression change in the reserpine-induced fibromyalgia-like rat is substantial and long-lasting.•Elevation of the RGS score in the reserpine-induced fibromyalgia-like rat may simulate spontaneous pain in patients with nociplastic pain.

SUBMITTER: Tanei S

PROVIDER: S-EPMC7078388 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1-S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.

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The method simulating spontaneous pain in patients with nociplastic pain using rats with fibromyalgia-like condition.

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