Preclinical Assessment of Inflammatory Pain

Abstract

While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis

“…Dynamic incapacitance is a measure of spontaneous pain that is associated with joint degeneration or inflammation arising from peripheral sensitisation. 4 , 28 In contrast, von Frey hairs were used to investigate evoked, reflexive responses (ie, paw withdrawal, shake, and lick) at a site distal to the injured joint. 28 This secondary allodynia is a consequence of central sensitisation in late stages of the MIA model, 16 and can be indicative of nerve injury.…”

Animal models of chronic pain: Advances and challenges for clinical translation

“…Several techniques have been developed to assess mechanical allodynia (e.g., von Frey filaments; Frey, ), mechanical hyperalgesia (e.g., Randall‐Selitto paw pressure apparatus; Randall and Selitto, ), and thermal hypersensitivity (radiant heat [e.g., Hargreaves apparatus; Hargreaves et al, ], acetone test [Yoon et al, ], hot–cold plate [Woolfe and Macdonald, ], and water bath [D'Amour and Smith, ]). Measurements of mechanical allodynia are particularly reliable for detecting altered nociceptive thresholds in nerve‐injured or chronically inflamed animals (Muley et al, ; Reitz et al, ). Traditionally, measures of thermal hyperalgesia involve the application of a constant, high‐threshold thermal stimulus (Bölcskei et al, ), and, although this technique has proved valuable for assessing the antinociceptive properties of analgesics, it can be unreliable for detecting lower nociceptive thresholds in animals with persistent pain (Lavich et al, ).…”

The Antinociceptive Activities of Certain NSAIDS Combinations in Murine Orofacial Test

“…The findings reported here are in agreement with previous works using formalin. So the antinociceptive activity of dexketoprofen was studied in mice using the formalin assay [7][8][9][10][11]. Also, antinociception induced by diclofenac, it has been reported [12].…”