Overview of Neurological Mechanism of Pain Profile Used for Animal “Pain-Like” Behavioral Study with Proposed Analgesic Pathways

Abstract

Pain is the most common sensation installed in us naturally which plays a vital role in defending us against severe harm. This neurological mechanism pathway has been one of the most complex and comprehensive topics but there has never been an elaborate justification of the types of analgesics that used to reduce the pain sensation through which specific pathways. Of course, there have been some answers to curbing of pain which is a lifesaver in numerous situations—chronic and acute pain conditions alike. This has been explored by scientists using pain-like behavioral study methodologies in non-anesthetized animals since decades ago to characterize the analgesic profile such as centrally or peripherally acting drugs and allowing for the development of analgesics. However, widely the methodology is being practiced such as the tail flick/Hargreaves test and Von Frey/Randall–Selitto tests which are stimulus-evoked nociception studies, and there has rarely been a complete review of all these methodologies, their benefits and its downside coupled with the mechanism of the action that is involved. Thus, this review solely focused on the complete protocol that is being adapted in each behavioral study methods induced by different phlogogenic agents, the different assessment methods used for phasic, tonic and inflammatory pain studies and the proposed mechanism of action underlying each behavioral study methodology for analgesic drug profiling. It is our belief that this review could significantly provide a concise idea and improve our scientists’ understanding towards pain management in future research.

Synergistic interaction between trazodone and gabapentin in rodent models of neuropathic pain

“…In the present study, we describe how the co-administration of low, ineffective doses of trazodone and gabapentin is active in reducing nociception both in an acute pain model in mice and in a chronic neuropathic assay in rats, in which a positive effect on the general well-being is also observed. Using the writhing test, which is an assay recommended for preliminary assessment of anti-nociceptive activity [ 28 ], we demonstrated through isobolographic analysis that trazodone and gabapentin exert a synergistic action on nociception and that ineffective doses of trazodone and gabapentin have a significant effect when they are co-administered. To explore the potential clinical relevance of these findings in chronic neuropathic pain conditions, we examined the effects of the trazodone and gabapentin combination in the CCI rat model.…”

Ulinastatin Exhibits Antinociception in Rat Models of Acute Somatic and Visceral Pain Through Inhibiting the Local and Central Inflammation

“…To help bridge the gap between preclinical knowledge and clinical management, several experimental animal models have been developed attempting to mimic human pathological pain syndrome. 26 By using two classical pain model, formalin and acetic acid-induced writhing test, we evaluated the antinociceptive effect of ulinastatin on acute somatic and visceral pain, and the underlying mechanisms were also investigated. We for the first time found that both the pre-administration and post-administration of ulinastatin could significantly attenuate intraplantar formalin injection-induced acute somatic pain in a dose-related manner, and the formalin-induced paw edema and ulcer were also improved by ulinastatin.…”

“…The first phase of activity (0–10 min; neurogenic pain) occurring immediately following injection reflects a direct activation of peripheral nociceptors, while the second phase of activity (15–60 min; inflammatory pain) is associated with the development of an inflammatory response and the release of nociceptive mediators which are responsible for sensitization of primary and spinal sensory neurons and subsequent activation of the nociceptors. 26 , 38 The inhibitory effect of ulinastatin on phase 2 of formalin test strongly suggested that its activity could be resultant from the anti-inflammatory action. Moreover, we found ulinastatin could also persistently inhibit formalin-induced paw edema and ulcer which corroborated the anti-inflammatory effect of ulinastatin.…”

Evaluation of Antinociceptive Effects of Chitosan-Coated Liposomes Entrapping the Selective Kappa Opioid Receptor Agonist U50,488 in Mice

“…The nociceptive visceral estimation was performed using the writhing test in order to evaluate the behavioral manifestations occurring as a reaction to the chemical noxious peritoneal irritation with 0.6% acetic acid (10 mL/kbw) [ 28 ].…”