Perioperative Anxiety and Stress Cortisol on Postoperative Pain: Pharmacological and Non-Pharmacological Management...

Postoperative pain remains a significant clinical challenge associated with delayed recovery, prolonged rehabilitation, and increased healthcare utilization. Despite advances in analgesic techniques, outcomes remain variable, suggesting that non-physical factors such as perioperative stress and anxiety play an important role. A relationship between perioperative anxiety, stress, and postoperative pain was examined with emphasis on physiologic mechanisms, assessment strategies, and management approaches. A narrative review was conducted using PubMed searches of the studies published in last 25 years. Search terms included cortisol, stress, perioperative surgery, postoperative pain, sex differences, questionnaires, and therapeutic interventions. Peer-reviewed studies involving human subjects were included if they evaluated perioperative stress, cortisol dynamics, postoperative pain, or related interventions. Preoperative anxiety is consistently associated with increased postoperative pain and higher analgesic requirements. Activation of the Hypothalamic-Pituitary-Adrenal Axis and subsequent cortisol release represents a key mechanism linking stress to pain modulation; however, significant variability limits the role of cortisol as a standalone biomarker. Validated tools such as the Brief Measure of Emotional Preoperative Stress, State-Trait Anxiety Inventory, and Hospital Anxiety and Depression Scale can identify high-risk patients but remain underutilized. Sex differences are evident, with women reporting higher pain scores and stronger associations between anxiety and postoperative pain. Non-pharmacological interventions, including music therapy and perioperative communication, demonstrate modest benefit, while pharmacological strategies show variable efficacy. Perioperative stress and anxiety significantly influence postoperative pain outcomes. A multimodal, patient-centered approach incorporating structured assessment and targeted interventions may improve recovery and optimize perioperative care.