Pathophysiology of Postoperative Pain

Segelcke, Daniel; Pogatzki-Zahn, Esther

doi:10.1016/b978-0-12-809324-5.24249-1

Cited by 7 publications

(9 citation statements)

References 188 publications

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“…Mechanical and heat hypersensitivity characteristics regarding intensity and time are consistent with previous results in this model. 63 Taken together, our behavior data suggest that POD 1 represents an appropriate time point to study proteome dynamics in incisional pain.…”

Section: Resultsmentioning

confidence: 61%

A proteome signature for acute incisional pain in dorsal root ganglia of mice

Pogatzki-Zahn

Gómez-Varela

Erdmann³

et al. 2021

Pain

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Section: Resultsmentioning

confidence: 61%

A proteome signature for acute incisional pain in dorsal root ganglia of mice

Pogatzki-Zahn

Gómez-Varela

Erdmann³

et al. 2021

Pain

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“…From a historical perspective, evoked pain-related behaviors are assessed by determining withdrawal reactions to external applied mechanical and thermal stimuli to the hindpaw of rodents. However, these assessments [still used in most preclinical pain studies (2,4,5)] are not only prone to experimental bias (6); they also encompass mainly the somatosensory (spinal reflex) pathways and miss the complex cognitive and emotional as well as voluntary components of pain. In contrast, multidimensional behavioral outcome measures in preclinical settings presumably capturing clinically relevant symptoms might improve translation (1,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

“…As a result, many patients suffer from acute and chronic pain as current analgesics have limited efficacy and side effects. One reason that hampers the development of new treatment options is a translational gap from basic science to the clinical situation ( 1 , 2 ). For example, there is increasing evidence for pain entity-specific mechanisms; therefore, the development and use of preclinical pain models, which more precisely represent clinical situations, are highly needed ( 1 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap

et al. 2021

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In recent years, preclinical pain research has failed to develop genuinely new analgesics for clinical use. This fact is reflected by a high number of patients, limited drug efficacy accompanied by side effects, and a long-term opioid intake. Two main aspects have been addressed, which hinder translation: the use of non-relevant pain models and a mismatch between pain-related outcomes in preclinical and clinical studies. Conversely, disease-specific pain models that mirror more closely the clinical situation and multidimensional behavioral outcome measures that objectively and reproducibly assess relevant pain-related symptoms in a preclinical setting could improve translation. Mechanistically, a matter of debate is the role of Ly6G+ neutrophil granulocytes (NGs) for pain. NGs are essential to eliminate pathogens and promote the wound healing process. For this purpose, there is a need to release various pro- and anti-inflammatory mediators, some of which could ameliorate or enhance pain. However, the contribution of NGs to different pain entities is contradictory for reflex-based tests, and completely unknown in the context of non-evoked pain (NEP) and movement-evoked pain (MEP). First, we combined withdrawal reflex-based assays with novel video-based assessments for NEP- and MEP-related behavior in two mouse pain models. The pain models utilized in this study were incision (INC) and pathogen/adjuvant-induced inflammation (CFA), translating well to postsurgical and inflammatory pain entities. Second, we depleted NGs and applied a set of behavioral assessments to investigate the role of NG migration in different pain modalities. Our comprehensive behavioral approach identified pain-related behaviors in mice that resemble (NEP) or differentiate (MEP) behavioral trajectories in comparison to mechanical and heat hypersensitivity, thereby indicating modality-dependent mechanisms. Further, we show that injury-induced accumulation of NGs minimally affects pain-related behaviors in both pain models. In conclusion, we report a novel assessment to detect NEP in mice after unilateral injuries using a more unbiased approach. Additionally, we are capable of detecting an antalgic gait for both pain entities with unique trajectories. The different trajectories between MEP and other pain modalities suggest that the underlying mechanisms differ. We further conclude that NGs play a subordinate role in pain-related behaviors in incisional and inflammatory pain.

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“…The inflammatory processes are diverse and trigger a prolonged hypersensitivity to evoked mechanical and heat but not to cold stimuli ( 24 ), directly around the incision injury (primary area of hypersensitivity). The primary hypersensitivity reaches a maximum shortly after awakening from anesthesia and is steadily reduced in the course of primary wound healing (depending on incision dimension) ( 10 , 11 ).…”

Section: Methodologies For the Wwhow Conceptmentioning

confidence: 99%

“…Unlike displacement and blunt preparations, incision always results in hemorrhage, direct activation of nociceptive fibers, and a distinct inflammatory response triggered by hemorrhage and cellular debris. These processes lead to the release of diverse damage-associated mediators, reactive oxygen species, pro-inflammatory mediators, activate residents, and facilitate the migration of immune cells, thereby altering the local tissue pH and further signaling cascades, including nociceptor sensitization ( 10 , 32 ). Compared to skin-only incision, these effects are massive and, thus, have a more pronounced influence on pain behavior ( 31 ), especially during muscle contraction for movement ( 33 ).…”

Section: Methodologies For the Wwhow Conceptmentioning

confidence: 99%

The “WWHow” Concept for Prospective Categorization of Post-operative Severity Assessment in Mice and Rats

et al. 2022

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The prospective severity assessment in animal experiments in the categories' non-recovery, mild, moderate, and severe is part of each approval process and serves to estimate the harm/benefit. Harms are essential for evaluating ethical justifiability, and on the other hand, they may represent confounders and effect modifiers within an experiment. Catalogs and guidelines provide a way to assess the experimental severity prospectively but are limited in adaptation due to their nature of representing particular examples without clear explanations of the assessment strategies. To provide more flexibility for current and future practices, we developed the modular Where-What-How (WWHow) concept, which applies findings from pre-clinical studies using surgical-induced pain models in mice and rats to provide a prospective severity assessment. The WWHow concept integrates intra-operative characteristics for predicting the maximum expected severity of surgical procedures. The assessed severity categorization is mainly congruent with examples in established catalogs; however, because the WWHow concept is based on anatomical location, detailed analysis of the tissue trauma and other intra-operative characteristics, it enables refinement actions, provides the basis for a fact-based dialogue with authority officials and other stakeholders, and helps to identify confounder factors of study findings.

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Pathophysiology of Postoperative Pain

Cited by 7 publications

References 188 publications

A proteome signature for acute incisional pain in dorsal root ganglia of mice

A proteome signature for acute incisional pain in dorsal root ganglia of mice

Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap

The “WWHow” Concept for Prospective Categorization of Post-operative Severity Assessment in Mice and Rats

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