Neurobiology of anesthetic-surgical stress and induced behavioral changes in dogs and cats: A review

Abstract

The anesthetic-surgical stress response consists of metabolic, neuroendocrine, hemodynamic, immunological, and behavioral adaptations through chemical mediators such as the adrenocorticotropic hormone, growth hormone, antidiuretic hormone, cortisol, aldosterone, angiotensin II, thyroid-stimulating hormone, thyroxine, triiodothyronine, follicle-stimulating hormone, luteinizing hormone, catecholamines, insulin, interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, and prostaglandin E-2. Behavioral changes include adopting the so-called prayer posture, altered facial expressions, hyporexia or anorexia, drowsiness, sleep disorders, restriction of movement, licking or biting the injured area, and vocalizations. Overall, these changes are essential mechanisms to counteract harmful stimuli. However, if uncontrolled surgical stress persists, recovery time may be prolonged, along with increased susceptibility to infections in the post-operative period. This review discusses the neurobiology and most relevant organic responses to pain and anesthetic-surgical stress in dogs and cats. It highlights the role of stress biomarkers and their influence on autonomous and demeanor aspects and emphasizes the importance of understanding and correlating all factors to provide a more accurate assessment of pain and animal welfare in dogs and cats throughout the surgical process.

Keywords: cats; dogs; neurobiology; pain; stress; welfare.

Figure-1

The hypothalamic-pituitary-adrenal axis and the response to surgical stress. ACTH=Adrenocorticotropic hormone, CRH=Corticotropin-releasing hormone, FSH=Follicle-stimulating hormone, GH=Growth hormone, GnRH=Gonadotropin-releasing hormone, K+=Potassium, LH=Luteinizing hormone, Na+=Sodium, RAA=Renin-angiotensin-aldosterone, TRH=Thyrotropin-releasing hormone, TSH=Thyroid-stimulating hormone, VP=Vasopressin [Source: 1,8,14,16].

Figure-2

Schematic of the neurobiological interaction between the hypothalamic-pituitary-adrenal axis, the metabolic changes, and the immune system after anesthetic-surgical stimuli. CNS=Central nervous system, CGRP=Calcitonin gen-related peptide, CRH=Corticotrophin-releasing hormone, IL=Interleukin, NO=Nitric oxide, PIVA=Partial intravenous anesthesia, PGE=Prostaglandin, TIVA=Total intravenous anesthesia, TNF=Tumor necrosis factor. Surgical stress, caused by tissue injury or anesthetic drugs, activates the HPA and hence the release of catecholamines and cortisol (known as stress hormones) in the adrenal gland. This action is controlled by factors such as CRH, VP, and ACTH in the pituitary gland. Under pathological states or persistent pain, the enhanced activity of cytokines (IL, TNF-α), PG, and NO can contribute to ischemia, inflammation, and coagulopathies. Together with the neurotransmitters coming from the CNS and spinal cord, this may result in additional damage [Source: 1,3,5,53,56,58].

Figure-3

Parasympathetic tone activity index monitoring for the assessment of pain. PTA uses the electrocardiogram signal to evaluate heart rate variability as a non-invasive method for assessing the autonomic nervous system. High-frequency waves (0.15-0.5 Hz) are observed in this figure, which are related only to parasympathetic activity. In this case, it was concluded that the patient did not experience pain.