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PAIN 155 (2014) 341–348
www.elsevier.com/locate/pain
Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: Comorbid pain matters Aslak Johansen a,b,⇑, Henrik Schirmer c,d, Audun Stubhaug e,f, Christopher S. Nielsen g a
Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway Department of Community Medicine, University of Tromsø, Norway c Division of Cardiothoracic and Respiratory Medicine, University Hospital of North Norway, Tromsø, Norway d Department of Clinical Medicine, University of Tromsø, Tromsø, Norway e Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway f Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway g Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 19 June 2013 Received in revised form 4 October 2013 Accepted 15 October 2013
Keywords: Persistent post-surgical pain Postoperative pain Chronic pain Comorbidity Pain sensitivity Pain tolerance Cold pressor test Epidemiology
a b s t r a c t In a large survey incorporating medical examination (N = 12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio = 1.34, 95% confidence interval = 1.08–1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N = 3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the coexistence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Ó 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction There is a growing awareness that persistent post-surgical pain (PPSP) is a health problem with extensive individual and social consequences [9,21,24,26]. Correlations between pain sensitivity and risk for development of PPSP have been reported. It has been suggested that individual differences in pain sensitivity may influence the risk for chronification of post-surgical pain [1,43], or that pain sensitivity may itself be influenced by changes in pain processing as a consequence of acute and persistent pain [25,39], or both [42]. Most studies of associations between pain sensitivity and surgical pain have focused on acute post-surgical pain, but ⇑ Corresponding author at: Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Postbox 100 Langnes, N-9038 Tromsø, Norway. Tel.: +47 77 66 91 56/97 59 93 47; fax: +47 77 62 61 92. E-mail address: [email protected] (A. Johansen).
some have linked risk of PPSP to increased sensitivity to experimental pain measures. In general, results have been conflicting [18,40]. Although PPSP is typically not classified in terms of pain quality or proposed mechanisms, it is often recognized as neuropathic pain [1,9,12,17,19,22,24,38]. Some surgical procedures, in particular, operations with high risk of nerve injury, have been associated with increased risk of PPSP and have gained special attention in the research literature [23,24,26,27]. Both regional pain before surgery [1,4] and remote preoperative pain unrelated to the actual surgery [4,8,15,35,36] are associated with PPSP, and one of the most consistent findings is that a high level of acute postoperative pain is predictive of subsequent PPSP [4,23,32,34,37]. The predominance of neuropathic pain, and the fact that the strongest predictor of pain is pain itself, may both indicate changes in central processing of pain as important contributors to PPSP development [7,23,41]. The idea of preemptive analgesia was
0304-3959/$36.00 Ó 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.pain.2013.10.013
342
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A. Johansen et al. / PAIN 155 (2014) 341–348
grounded on this hypothesis, that is, that attenuating or blocking of nociceptive input could prevent central sensitization and thereby reduce the risk for PPSP. However, the efficacy of such an approach remains to be proved [10,23,24]. With data from a large population-based survey including experimental pain assessments, we aimed to investigate whether individuals with PPSP had signs of enhanced pain sensitivity or reduced pain tolerance compared to pain-free individuals and individuals with chronic pain from other causes. 2. Methods 2.1. Study population and sample—the Tromsø Study In 2007 to 2008, a total of 12,981 from among 19,762 invited individuals attended the sixth wave of the Tromsø Study (Tromsø VI), a cross-sectional survey and medical examination in North Norway. All inhabitants 40 to 42 years and 60 to 87 years old were invited, along with 10% to 40% random samples of other age groups more than 30 years of age. Women constituted 53.4% of the attendants, and 51.3% of the invited. An overview of the recruitment procedures, response rates, and sample composition has been published previously [20]. Tromsø VI addressed a wide range of health problems, including cardiovascular and cerebrovascular diseases, dermatological, rheumatological, neurological, psychiatric, and work related disorders, osteoporosis, and chronic pain. 2.2. Questionnaires All participants completed 2 questionnaires. The first, 4-page questionnaire was distributed together with the invitation and completed before attending the examination. A second, more comprehensive questionnaire was either filled in during the visit or completed later at home and returned by mail. The first questionnaire included the question, ‘‘Do you have persistent or constantly recurring pain that has lasted for 3 months or more?’’ In the following, participants who responded ‘‘yes’’ to this question will be referred to as having chronic pain (Fig. 1a). The individuals with chronic pain were asked to complete follow-up questions in the second questionnaire, covering, among other items, pain duration and intensity, as well as the supposed cause of the pain. For the latter, they were asked, ‘‘What do you believe is the cause of the pain?’’ Responses to this question were provided by ticking 1 or more of the following 18 predefined categories: accident/acute injury, long-term stress, surgery, herniated disk, whiplash, migraine/headache, osteoarthritis, rheumatoid arthritis, Bechterews syndrome, fibromyalgia, angina, poor blood circulation, cancer, nerve damage/neuropathy, infection, herpes zoster, other cause, or do not know. Independent of the question about chronic pain, participants were asked, ‘‘Have you during the past 3 years undergone surgery?’’ (Fig. 1a). Individuals answering ‘‘yes’’ to this question, were asked to complete follow-up questions about surgery, including time from surgery, present sensory abnormalities in the surgical area, and present intensity of pain in the surgical area. For both chronic pain and pain in the surgical area, pain intensity was graded by applying an 11-point numerical rating scale (NRS) with 0 = no pain and 10 = the most intense pain imaginable as the anchors. Sensory abnormalities were identified by 3 questions addressing reduced sensitivity (hypoesthesia), increased sensitivity to painful stimuli (hyperalgesia) or painful sensations from innocuous stimuli (allodynia), respectively. The presence of hyperalgesia and/or allodynia in the surgical area is referred to as ‘‘hyperesthesia’’ below. Those individuals who had gone through more than 1 surgical procedure were asked to respond with
reference to the last procedure. Results on the prevalence of persistent pain, anatomic locations of surgery, and sensory disturbances have previously been published [21]. 2.3. Persistent post-surgical pain In a previous report [21], we pointed out that specific questions about persistent, localized pain resulted in higher prevalence estimates of PPSP than did more general questions about persistent pain. We therefore decided to apply 2 different methods of identifying PPSP in this report (Fig. 1b): I. Individuals with chronic pain were categorized according to their responses to the question on assumed cause of the chronic pain. As ticking multiple causes was an option, we constructed 2 variables that, in combination, could identify individuals with pain from surgery with and without pain from other causes: a. Chronic pain from surgery: Chronic pain where surgery is indicated as a cause, alone or in combination with other causes. b. Other chronic pain: Chronic pain from all other causes than surgery alone. The distribution of individuals when combining these 2 categorical variables is presented in Table 1 and illustrated in Fig. 1b, column I. II. Among the participants who reported surgery in the preceding 3 years, individuals where less than 3 months had elapsed since the surgery were excluded from analysis (Fig. 1b, column II). The remaining 1661 were categorized into 4 groups in accordance to their ratings of present, maximum pain intensity in the surgical area; no pain (NRS score 0), mild pain (NRS 1–3), moderate pain (NRS 4–6), and severe pain (NRS 7–10). 2.4. Experimental pain assessments The intended sample included all subjects participating in the sixth wave of the Tromsø Study (N = 12,981). However, because of capacity limitations during peak hours, technical problems, or technicians’ sick leave, some subjects were not examined. In these cases, the technicians were asked to prioritize subjects
PAIN 155 (2014) 341–348
www.elsevier.com/locate/pain
Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: Comorbid pain matters Aslak Johansen a,b,⇑, Henrik Schirmer c,d, Audun Stubhaug e,f, Christopher S. Nielsen g a
Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Tromsø, Norway Department of Community Medicine, University of Tromsø, Norway c Division of Cardiothoracic and Respiratory Medicine, University Hospital of North Norway, Tromsø, Norway d Department of Clinical Medicine, University of Tromsø, Tromsø, Norway e Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University Hospital, Rikshospitalet, Oslo, Norway f Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway g Division of Mental Health, Norwegian Institute of Public Health, Oslo, Norway b
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
a r t i c l e
i n f o
Article history: Received 19 June 2013 Received in revised form 4 October 2013 Accepted 15 October 2013
Keywords: Persistent post-surgical pain Postoperative pain Chronic pain Comorbidity Pain sensitivity Pain tolerance Cold pressor test Epidemiology
a b s t r a c t In a large survey incorporating medical examination (N = 12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio = 1.34, 95% confidence interval = 1.08–1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N = 3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the coexistence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Ó 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
1. Introduction There is a growing awareness that persistent post-surgical pain (PPSP) is a health problem with extensive individual and social consequences [9,21,24,26]. Correlations between pain sensitivity and risk for development of PPSP have been reported. It has been suggested that individual differences in pain sensitivity may influence the risk for chronification of post-surgical pain [1,43], or that pain sensitivity may itself be influenced by changes in pain processing as a consequence of acute and persistent pain [25,39], or both [42]. Most studies of associations between pain sensitivity and surgical pain have focused on acute post-surgical pain, but ⇑ Corresponding author at: Division of Surgical Medicine and Intensive Care, University Hospital of North Norway, Postbox 100 Langnes, N-9038 Tromsø, Norway. Tel.: +47 77 66 91 56/97 59 93 47; fax: +47 77 62 61 92. E-mail address: [email protected] (A. Johansen).
some have linked risk of PPSP to increased sensitivity to experimental pain measures. In general, results have been conflicting [18,40]. Although PPSP is typically not classified in terms of pain quality or proposed mechanisms, it is often recognized as neuropathic pain [1,9,12,17,19,22,24,38]. Some surgical procedures, in particular, operations with high risk of nerve injury, have been associated with increased risk of PPSP and have gained special attention in the research literature [23,24,26,27]. Both regional pain before surgery [1,4] and remote preoperative pain unrelated to the actual surgery [4,8,15,35,36] are associated with PPSP, and one of the most consistent findings is that a high level of acute postoperative pain is predictive of subsequent PPSP [4,23,32,34,37]. The predominance of neuropathic pain, and the fact that the strongest predictor of pain is pain itself, may both indicate changes in central processing of pain as important contributors to PPSP development [7,23,41]. The idea of preemptive analgesia was
0304-3959/$36.00 Ó 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.pain.2013.10.013
342
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A. Johansen et al. / PAIN 155 (2014) 341–348
grounded on this hypothesis, that is, that attenuating or blocking of nociceptive input could prevent central sensitization and thereby reduce the risk for PPSP. However, the efficacy of such an approach remains to be proved [10,23,24]. With data from a large population-based survey including experimental pain assessments, we aimed to investigate whether individuals with PPSP had signs of enhanced pain sensitivity or reduced pain tolerance compared to pain-free individuals and individuals with chronic pain from other causes. 2. Methods 2.1. Study population and sample—the Tromsø Study In 2007 to 2008, a total of 12,981 from among 19,762 invited individuals attended the sixth wave of the Tromsø Study (Tromsø VI), a cross-sectional survey and medical examination in North Norway. All inhabitants 40 to 42 years and 60 to 87 years old were invited, along with 10% to 40% random samples of other age groups more than 30 years of age. Women constituted 53.4% of the attendants, and 51.3% of the invited. An overview of the recruitment procedures, response rates, and sample composition has been published previously [20]. Tromsø VI addressed a wide range of health problems, including cardiovascular and cerebrovascular diseases, dermatological, rheumatological, neurological, psychiatric, and work related disorders, osteoporosis, and chronic pain. 2.2. Questionnaires All participants completed 2 questionnaires. The first, 4-page questionnaire was distributed together with the invitation and completed before attending the examination. A second, more comprehensive questionnaire was either filled in during the visit or completed later at home and returned by mail. The first questionnaire included the question, ‘‘Do you have persistent or constantly recurring pain that has lasted for 3 months or more?’’ In the following, participants who responded ‘‘yes’’ to this question will be referred to as having chronic pain (Fig. 1a). The individuals with chronic pain were asked to complete follow-up questions in the second questionnaire, covering, among other items, pain duration and intensity, as well as the supposed cause of the pain. For the latter, they were asked, ‘‘What do you believe is the cause of the pain?’’ Responses to this question were provided by ticking 1 or more of the following 18 predefined categories: accident/acute injury, long-term stress, surgery, herniated disk, whiplash, migraine/headache, osteoarthritis, rheumatoid arthritis, Bechterews syndrome, fibromyalgia, angina, poor blood circulation, cancer, nerve damage/neuropathy, infection, herpes zoster, other cause, or do not know. Independent of the question about chronic pain, participants were asked, ‘‘Have you during the past 3 years undergone surgery?’’ (Fig. 1a). Individuals answering ‘‘yes’’ to this question, were asked to complete follow-up questions about surgery, including time from surgery, present sensory abnormalities in the surgical area, and present intensity of pain in the surgical area. For both chronic pain and pain in the surgical area, pain intensity was graded by applying an 11-point numerical rating scale (NRS) with 0 = no pain and 10 = the most intense pain imaginable as the anchors. Sensory abnormalities were identified by 3 questions addressing reduced sensitivity (hypoesthesia), increased sensitivity to painful stimuli (hyperalgesia) or painful sensations from innocuous stimuli (allodynia), respectively. The presence of hyperalgesia and/or allodynia in the surgical area is referred to as ‘‘hyperesthesia’’ below. Those individuals who had gone through more than 1 surgical procedure were asked to respond with
reference to the last procedure. Results on the prevalence of persistent pain, anatomic locations of surgery, and sensory disturbances have previously been published [21]. 2.3. Persistent post-surgical pain In a previous report [21], we pointed out that specific questions about persistent, localized pain resulted in higher prevalence estimates of PPSP than did more general questions about persistent pain. We therefore decided to apply 2 different methods of identifying PPSP in this report (Fig. 1b): I. Individuals with chronic pain were categorized according to their responses to the question on assumed cause of the chronic pain. As ticking multiple causes was an option, we constructed 2 variables that, in combination, could identify individuals with pain from surgery with and without pain from other causes: a. Chronic pain from surgery: Chronic pain where surgery is indicated as a cause, alone or in combination with other causes. b. Other chronic pain: Chronic pain from all other causes than surgery alone. The distribution of individuals when combining these 2 categorical variables is presented in Table 1 and illustrated in Fig. 1b, column I. II. Among the participants who reported surgery in the preceding 3 years, individuals where less than 3 months had elapsed since the surgery were excluded from analysis (Fig. 1b, column II). The remaining 1661 were categorized into 4 groups in accordance to their ratings of present, maximum pain intensity in the surgical area; no pain (NRS score 0), mild pain (NRS 1–3), moderate pain (NRS 4–6), and severe pain (NRS 7–10). 2.4. Experimental pain assessments The intended sample included all subjects participating in the sixth wave of the Tromsø Study (N = 12,981). However, because of capacity limitations during peak hours, technical problems, or technicians’ sick leave, some subjects were not examined. In these cases, the technicians were asked to prioritize subjects
