Acute and Chronic Effects of Postoperative Pain

Uncontrolled postoperative pain may produce a range of detrimental acute and chronic effects (see Chapter 73 ). Attenuation of perioperative pathophysiology that occurs during surgery through reduction of nociceptive input into the CNS and optimization of perioperative analgesia may decrease complications and facilitate the patient's recovery during the immediate postoperative period^[18] and after discharge from the hospital.

Acute Effects

The perioperative period is associated with a variety of pathophysiologic responses that may be initiated or maintained by nociceptive input. Although these responses may have had a beneficial teleologic purpose, the same response to the iatrogenic nature of modern day surgery may be harmful. Uncontrolled perioperative pain may potentiate some of these perioperative pathophysiologies and increase morbidity and mortality for patients. Attenuation of postoperative pain, especially using certain types of analgesic regimens, may decrease perioperative morbidity and mortality. ^[19]

The transmission of nociceptive stimuli from the periphery to the CNS results in the neuroendocrine stress response, a combination of local inflammatory substances (e.g., cytokines, prostaglandins, leukotrienes) and systemic mediators of the neuroendocrine response. The dominant neuroendocrine responses to pain involve hypothalamic-pituitary-adrenocortical and sympathoadrenal interactions. Suprasegmental reflex responses to pain result in increased sympathetic tone, increased catecholamine and catabolic hormone secretion (e.g., cortisol, adrenocorticotropic hormone, antidiuretic hormone, glucagon, aldosterone, renin, angiotensin II), and decreased secretion of anabolic hormones.^[20] The effects include sodium and water retention and increased levels of blood glucose, free fatty acids, ketone bodies, and lactate. A hypermetabolic, catabolic state occurs as metabolism and oxygen consumption are increased and metabolic substrates are mobilized from storage depots.^[20] The extent of the stress response is influenced by many factors, including the type of anesthesia and intensity of surgical injury with the extent of stress response proportional to degree of surgical trauma. ^[21] The negative nitrogen balance and protein catabolism may impede the patient's convalescence; however, attenuation of the stress response and postoperative pain may facilitate and accelerate the patient's recovery postoperatively.

The neuroendocrine stress response may potentiate detrimental physiologic effects in other areas of the body. The stress response may be an important factor in the postoperative development of hypercoagulability.^[19] Enhancement of coagulation (i.e., decreased levels of natural anticoagulants and increased levels of procoagulants), inhibition of fibrinolysis, and increased platelet reactivity and plasma viscosity^[22] may contribute to an elevated incidence of postoperative hypercoagulable-related events such as deep venous thrombosis, vascular graft failure, and myocardial ischemia.^[23] The stress response also may potentiate postoperative immunosuppression, the extent of which correlates to the severity of surgical injury.^[21] Hyperglycemia from the stress response may contribute to poor wound healing and depression of immune function.^[24]

Uncontrolled postoperative pain may activate the sympathetic nervous system, which may contribute to morbidity or mortality. Sympathetic activation may increase

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Nociceptors that are activated after surgical trauma may initiate several detrimental spinal reflex arcs. Postoperative respiratory function is markedly decreased, especially after upper abdominal and thoracic surgery. Spinal reflex inhibition of phrenic nerve activity is an important component of this decreased postoperative pulmonary function.^[27] However, control of postoperative pain is also important, because patients with poor pain control may breathe less deeply, have an inadequate cough, and may be more likely to develop postoperative pulmonary complications.^[28] Nociceptor activation may also initiate a spinal reflex inhibition of gastrointestinal tract function and delay return of gastrointestinal motility.^{[19] [23]}

Many detrimental pathophysiologic effects occur in the perioperative period and are associated with activation of nociceptors and the stress response. Uncontrolled pain may result in sympathetic nervous system activation, causing a variety of potentially harmful physiologic responses that may adversely influence the extent of morbidity and mortality for patients. Nociceptor activation may also result in several detrimental inhibitory spinal reflexes. Control of the pathophysiologic processes associated with acute postoperative pain may attenuate the stress response, sympathetic outflow, and inhibitory spinal reflexes and may lead to improvements in morbidity, mortality, and other nontraditional outcomes (e.g., health-related quality of life, patient satisfaction).^[23]

Chronic Effects

Poorly controlled acute postoperative pain may be an important predictive factor in the development of pathologic long-term chronic pain after surgery. ^{[17] [29]} Although the issue of whether acute pain directly causes chronic pain is relatively controversial, increasing experimental and clinical evidence suggests that the transition from acute to chronic pain occurs very quickly and that long-term behavioral and neurobiologic changes occur much earlier than previously anticipated.^[10] Chronic pain is relatively common after procedures such as limb amputation (30% to 83%), thoracotomy (22% to 67%), sternotomy (27%), breast surgery (11% to 57%), and gallbladder surgery (up to 56%).^{[17] [30]} Studies suggest that the severity of acute postoperative pain may be an important predictor in the development of chronic pain after breast surgery,^[16] thoracic surgery,^{[14] [15] [31]} hernia repair,^[32] amputation,^[33] and gallbladder surgery.^{[17] [34]} Based on our understanding of the neurobiology of nociception, it is possible to see how continued peripheral nociceptive input from surgical injury could maintain central sensitization and chronic pain. Prevention of central sensitization and control of postoperative pain may decrease the incidence of chronic pain.^{[35] [36]}

Control of acute postoperative pain may improve long-term recovery or patient-oriented outcomes (e.g., quality of life). Patients whose pain is controlled in the early postoperative period (especially with use of continuous epidural or peripheral catheter techniques) may be able to actively participate in postoperative rehabilitation, which may improve short- and long-term recovery after surgery.^{[37] [38]} Optimizing treatment of acute postoperative pain can improve health-related quality of life (HRQL).^{[39] [40]} Postoperative chronic pain that develops as a result of poor postoperative pain control^[17] may interfere with patients' activities of daily living.^[41]