From acute to chronic postsurgical pain: the significance of the acute pain response.

The thesis comprises an overview and four papers, all published or submitted for publication in international peer-reviewed scientific journals. Chronic pain after surgery is a common and debilitating complication after many types of surgery. The cause and pathology behind is still mainly uncovered, though several risk factors have been proposed. One of the strongest risk factors for persistent postsurgical pain is the intensity of the acute pain response though the mechanisms involved remain unsettled. The acute pain response consists of several different types of pain (i.e. somatic pain, visceral pain, referred pain, neuropathic pain). It's uncovered whether some components of the acute pain response are closer correlated to chronic pain than others and whether treatment of acute pain can change the risk of developing chronic pain. The aim of the thesis was to investigate which components of the acute pain response, was correlated to chronic postsurgical pain in patients for cholecystectomy and lobectomy. Furthermore, to study the type and time course of ipsilateral shoulder pain after lobectomy and whether an ultrasound-guided supraclavicular phrenic nerve block was effective in preventing acute and chronic shoulder pain after major thoracic surgery. Paper I is based on a prospective, observational, multicenter, cohort study, in which 100 patients for cholecystectomy was examined preoperatively, 1 week postoperatively and 3, 6, and 12 months postoperatively for pain, psychological factors and signs of hypersensitivity. Paper II and III are based on a prospective, observational, cohort study, in which 60 patients for lobectomy ware examined preoperatively, 4 days postoperatively and 12 months postoperatively for pain, psychological factors and signs of hypersensitivity. Paper IV is based on a prospective, randomized, double-blind and placebo-controlled trial, where 76 patients were randomized to receive ultrasound guided supraclavicular phrenic nerve block with a blinded study solution (ropivacaine or saline). The primary endpoint was pain within the first 6 hours after surgery. Secondary endpoints included pain the following days and after 3 months. Paper I: Nine patients developed chronic unexplained pain 12 months postoperatively. In a multivariate analysis, cumulated visceral pain during the first week and number of preoperative biliary pain attacks were identified as independent risk factors for unexplained pain 12 months after surgery. There were no consistent signs of increased hypersensitivity in the referred pain area before or after the operation in patients with chronic pain. Paper II: Sixteen patients developed chronic pain 12 months postoperatively. In a multivariate analysis thoracic pain during activity was the only significant predictor of chronic pain 12 months after surgery. Shoulder pain, referred pain and overall pain was not significant predictors. There were no signs of general hypersensitivity 12 months after surgery. Paper III: Forty-seven (78%) of patients experienced postoperative shoulder pain, but only 25 patients (42%) experienced clinically relevant pain (NRS > 3). On postoperative day 4, 19 (32%) of patients suffered shoulder pain, but only 4 (7%) suffered clinically relevant pain. Only 4 patients (8%) suffered chronic shoulder pain. Ipsilateral shoulder pain of the musculoskeletal type is more intense than referred ipsilateral shoulder pain, though referred shoulder pain is more common. Surgical approach was not related to incidence of shoulder pain or type of pain. Paper IV: Shoulder pain within 6 hours of the operation was reported in 9 patients (24%) in the treatment group versus 26 (68%) in the placebo group (p<0.0001). Absolute and relative risk reductions were 44% (95% CI 22-67%) and 65% (95% CI 41-80%), respectively. No major complications, including respiratory compromise, were observed. Subsequent treatment with a nerve catheter was effective during the first 36 hours after surgery, but because of loss of nerve catheter or early submission of patients, data concerning pain the following days and after 3 months were inconclusive.