Background: According to earlier studies where the main aim has been quality of life, there is growing evidence of increased levels of persistent pain in survivors of critical illness. The cause of admission and several factors during intensive care may have associated risk factors for pain persistence. This systematic review aims to determine the incidence or prevalence of persistent pain after critical illness and to identify risk factors for it. Methods: Six databases were searched, and eventually nine studies were included in the final systematic process. The validity of observational and cross-sectional studies was analysed using the National Institute of Health 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. Results: The incidence of persistent pain after intensive care varied from 28% to 77%. Risk factors for persistent pain were acute pain at discharge from ICU, higher thoracic trauma score, surgery, pre-existing pain, organ failure, longer length of ventilator or hospital stay, and sepsis. No difference in incidence between medical and surgical patients was found. Conclusions: New systematic, observational studies are warranted to identify persistent pain-related factors in intensive care to improve pain management protocols and thereby diminish the risk of persistent pain after ICU stay.

Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB1*04 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB1*03:02 allele together with DRB1*04 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n=258), where carriers of the DQB1*03:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB1*04 - DQB1*03:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms.

In the Swedish Hernia Register 2834 inguinal hernia repairs in 2583 patients were registered in the county of Uppsala 1998-2004. In May 2005 the 2421 patients still alive were requested by mail to fill in a validated questionnaire concerning postherniorrhaphy pain. The final response rate became 72%. Altogether 519 patients (29%) stated that they had pain in the operated groin to some extent during past week. In 98 patients (6%) the pain interfered with daily activities. Factors associated with an increased risk of residual pain in a multivariate logistic regression analysis were age below median, operation for recurrence, open repair technique, history of preoperative pain, and less than three years from surgery. Factors not associated with occurrence of residual pain were gender, method of anaesthesia during surgery, hernia sac diameter, postoperative complications, hernia type, need for emergency operation, reducibility of the hernia sac and complete dissection of the hernia sac. Factors found to be associated with impairment of function due to pain in a multivariate logistic regression analysis were: age below median, female gender, medial hernia, open repair technique, postoperative complications, need for operation for recurrence, presence of preoperative pain and less than three years from surgery. The possibility of long-term pain as an outcome after hernia operations should be taken into consideration in the decision making prior to operation.