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A case of scrotal pain associated with genitofemoral nerve injury following cystectomy
Journal of Clinical Anesthesia (2016) 32, 150–152
Case report
A case of scrotal pain associated with genitofemoral nerve injury following cystectomy Tetsuya Sakai MD, PhD ⁎, Hiroaki Murata MD, PhD, Tetsuya Hara MD, PhD Department of Anesthesiology, Nagasaki University School of Medicine Received 29 December 2014; revised 27 January 2016; accepted 16 February 2016
Keywords: Genitofemoral nerve; Pelvic lymphadenectomy and pregabalin; Postoperative neuropathy; Radical cystectomy
Abstract The genitofemoral neuropathy is one of the most common causes of groin pain after surgery. Especially, the groin pain induced by genitofemoral nerve injury during herniorrhaphy is a well-known complication. In contrast, much attention is not paid for groin pain induced by genitofemoral nerve injury after pelvic surgery, and there have been few reports in males, although it has been reported in females. We report a 59-year-old male patient who suffered from scrotal pain caused by presumed genitofemoral nerve injury during radical cystectomy and bilateral pelvic lymphadenectomy for bladder cancer. The surgical procedure was performed in a supine position under general anesthesia, without epidural anesthesia. Postoperatively, he complained of burning and lancinating pain in bilateral scrotal area. Abnormal findings were not evident using computed tomography and ultrasonography of the pelvis, including the scrotum and testicles. He had severe allodynia of the ventral scrotum and bilateral ventromedial thigh region, with absence of cremasteric reflex. We speculated that his pain might have been surgery-induced genitofemoral neuropathy, which was caused by nerve injury during lymphadenectomy near the external iliac vessels. His scrotal pain and allodynia following the cystectomy were partially and gradually relieved after administering pregabalin, further supporting the contention that his scrotal pain was a surgery-induced neuropathy. © 2016 Elsevier Inc. All rights reserved.
1. Introduction The genitofemoral neuropathy is one of the most common causes of groin pain encountered in clinical practice [1–4]. The genitofemoral neuropathy is basically caused by the genitofemoral nerve injury anywhere along its path, including iatrogenic direct trauma to the nerve, as well as damage during inguinal herniorrhaphy [3], varicocelectomy [4], pelvic surgery [1,2], and sympathetic nerve block procedure [5], although it may rarely occur idiopathically [6,7]. Especially, the groin pain induced by genitofemoral nerve injury during herniorrhaphy is a well-known complication. This pain is lancinating and radiates ⁎ Corresponding author at: Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Tel.: +81 95 819 7370; fax: +81 95 819 7373. E-mail address: [email protected] (T. Sakai). http://dx.doi.org/10.1016/j.jclinane.2016.02.022 0952-8180/© 2016 Elsevier Inc. All rights reserved.
to the groin area, including the ventral scrotum in males [3,8]. In contrast, much attention is not paid for groin pain induced by genitofemoral nerve injury after pelvic surgery in males and there have been few reports, although it has been reported in females [1]. We report such a patient who suffered from scrotal pain caused by presumed genitofemoral neuropathy following cystectomy. We took an opportunity of this report to review the causes, circumstances, and diagnosis about postoperative genitofemoral neuropathy.
2. Case report Three months ago, a 59-year-old (body weight, 69 kg; height, 169 cm) man underwent radical cystectomy and bilateral pelvic lymphadenectomy for bladder cancer. He had no
Neuropathic scrotal pain following cystectomy
151
Quadratus lumborum muscle
Genitofemoral nerve
Psoas muscle Presumed genitofemoral nerve injury point External iliac vessel
Ilioinguinal nerve
Genital branch of genitofemoral nerve
Femoral branch of genitofemoral nerve
Fig. 1
Courses of the genitofemoral and ilioinguinal nerves and the external iliac vessels.
medical history, including diabetes mellitus and neuropathy, and result of neurologic examination was normal at admission. The surgical procedure was performed with the patient in a supine position under general anesthesia, without any peripheral/ central nerve block. The duration of the surgery was 8 hours. On postoperative day 1, he complained of burning and lancinating pain in bilateral scrotal area. Abnormal findings were not observed using computed tomography and ultrasonography of the abdomen and pelvis, including the scrotum, testicles, prostate, and epididymis. Results of lumbar spine magnetic resonance imaging and brain computed tomography were equally unremarkable. His pain with hyperalgesia was exacerbated by wearing underwear and walking and hip extension. He was referred to our clinic 2 months after surgery because the prescribed anti-inflammatory analgesics were ineffective. The intensity of his scrotal pain was 10 (on a 010 numerical rating scale), and a neurologic examination showed severe allodynia with hyperalgesia and dysesthesia in bilateral ventral scrotal and ventromedial thigh regions, with a right-side dominance. Tapping the skin immediately proximal to the pubic tubercle on a line linking the anterior superior iliac spine to the pubic symphysis elicited the scrotal pain. The bilateral cremasteric reflex was absent. The patient did not have any motor weakness, dysuria, and dyschezia. On the basis of his sign and symptom, we speculated that his pain might have been surgery-induced genitofemoral neuropathy, which
was caused by nerve injury during lymphadenectomy near the external iliac vessels, resulting in the described scrotal pain (Fig. 1). Initially, we prescribed pregabalin (75 mg/d), and within a week, his scrotal pain intensity had decreased to 5 and he was very satisfied with the analgesic effect of pregabalin. The patient continued taking flexible-dose pregabalin based on tolerability (25-150 mg/d taken once or twice daily) for 7 months; at that time, his pain and allodynia were greatly diminished, and then pregabalin was stopped (Fig. 2).
3. Discussion In this case, the patient's scrotal pain is likely to have been induced by genitofemoral nerve injury during lymphadenectomy near the external iliac vessels. The diagnosis was assessed based on his painful area that corresponded to the domain innervated by the genital branch of genitofemoral nerve, the absence of cremasteric reflex, and the normal image findings at central/spinal level. The genitofemoral nerve originates from L1 and L2 and emerges from the psoas muscle. It runs along the ventral surface of the psoas muscle and divides into the genital and femoral branches. The genital branch crosses over to the external iliac vessels in the pelvis and then supplies motor fiber to the cremasteric muscle and sensory fibers to the skin of the ventral scrotum and upper inner thighs, with a dominance of scrotum [9–12].
NRS
Pregabalin (mg/day)
10
150
100 5 50
0
0 0
10
20
30
Time (weeks) after starting pregabalin therapy
Fig. 2
Time course of numerical rating scale (NRS) of scrotal pain and the dose of pregabalin. Open circle, NRS; closed triangle, pregabalin dose.
152 The groin area receives sensory innervation not only from genitofemoral but also from the ilioinguinal nerves [9,10]. Given the area of the pain and allodynia described in the present case, we had to diagnose which nerve of ilioinguinal or genitofemoral might have been injured during the surgery. The ilioinguinal nerve also innervates the skin of the ventral scrotum and upper inner thighs same as the genitofemoral nerve, and these nerves sometimes overlap each other, making discrimination between the nerves difficult [9,10]. The ilioinguinal and genitofemoral nerves are known to be easily injured intraoperatively at the level of inguinal canal, lower abdomen, and retroperitoneum. Commonly, nerve injuries at the levels of inguinal canal or lower abdomen are observed after herniorrhaphy [3] or extended transverse incisions, such as Pfannenstiel incisions, respectively [8]. The present patient underwent surgery involving the abdominal median section. Although the ilioinguinal nerve also emerges from the lateral border of the psoas muscle, it passes obliquely across the quadratus lumborum [11]. Because the quadratus lumborum is located lateral and dorsal to the psoas muscle, the ilioinguinal nerve is not more likely to be injured than the genitofemoral nerve at the level of retroperitoneum. Large pelvic surgeries, with or without radical lymphadenectomies, are known to result in injury to the nerves coursing through the pelvis, especially when lymphadenectomy is performed [1,2]. In addition, the cremasteric reflex was absent in the patient. Therefore, we speculate that the genital branch of genitofemoral nerve was affected during lymphadenectomy near the external iliac vessels at the level of retroperitoneum. Some diagnostic approaches, including selective nerve block and electromyography, are suggested to distinguish which nerve of ilioinguinal or genitofemoral nerve is damaged [8,12]. We also proposed to the patient to undergo these approaches for diagnosis. However, the patient was satisfied with the oral medication and refused additional diagnostic tests. Among antiepileptic drugs (gabapentin and pregabalin) recommended as first-line treatment for neuropathic pain, pregabalin was chosen in accordance with our institution practice. Neuropathic pain has been defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [13,14]. In the present case, pregabalin partially and gradually improved the patient's postcystectomy scrotal pain 1 week after administration, also suggesting that the scrotal pain described in the present case report was surgery-induced neuropathic pain. In addition, pregabalin has sedative and antianxious effects [14,15]. Negative psychic symptoms, especially anxiety, are thought to be causes to exacerbate a pain. We speculate that pregabalin improved his
T. Sakai et al. anxiety directly, which may have contributed to alleviate his pain indirectly [16,17]. In conclusion, our report shows that postoperative scrotal pain caused by the genitofemoral neuropathy may occur following radical cystectomy, with lymphadenectomy near the external iliac vessels.
References [1] Cardosi RJ, Cox CS, Hoffman MS. Postoperative neuropathies after major pelvic surgery. Obstet Gynecol 2002;100:204. [2] Irvin W, Andersen W, Taylor P, Rice L. Minimizing the risk of neurologic injury in gynecologic surgery. Obstet Gynecol 2004;103:374-82. [3] Ducic I, Dellon AL. Testicular pain after inguinal hernia repair: an approach to resection of the genital branch of genitofemoral nerve. J Am Coll Surg 2004;198:181-4. [4] Muensterer OJ. Genitofemoral nerve injury after laparoscopic varicocelectomy in adolescents. J Urol 2008;180:2155-8. [5] Sayson SC, Ramamurthy S, Hoffman J. Incidence of genitofemoral nerve block during lumbar sympathetic block: comparison of two lumbar injection sites. Reg Anesth 1997;22:569-74. [6] Rischbieth RH. Genito-femoral neuropathy. Clin Exp Neurol 1986;22: 145-7. [7] O'Brien MD. Genitofemoral neuropathy. Br Med J 1979;21:1052. [8] ter Meulen BC, Peters EW, Wijsmuller A, Kropman RF, Mosch A, Tavy DL. Acute scrotal pain from idiopathic ilioinguinal neuropathy: diagnosis and treatment with EMG-guided nerve block. Clin Neurol Neurosurg 2007;109:535-7. [9] Sasaoka N, Kawaguchi M, Yoshitani K, Kato H, Suzuki A, Furuya H. Evaluation of genitofemoral nerve block, in addition to ilioinguinal and iliohypogastric nerve block, during inguinal hernia repair in children. Br J Anaesth 2005;94:243-6. [10] Rab M, Ebmer And J, Dellon AL. Anatomic variability of the ilioinguinal and genitofemoral nerve: implications for the treatment of groin pain. Plast Reconstr Surg 2001;108:1618-23. [11] Mirilas P, Skandalakis JE. Surgical anatomy of the retroperitoneal spaces, part IV: retroperitoneal nerves. Am Surg 2010;76:253-62. [12] Cesmebasi A, Yadav A, Gielecki J, Tubbs RS, Loukas M. Genitofemoral neuralgia: a review. Clin Anat 2015;28:128-35. [13] O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med 2009;122:S22-32. [14] Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85:S3-14. [15] Darbà J, Kaskens L, Pérez C, Álvarez E, Navarro-Artieda R, SicrasMainar A. Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. Adv Ther 2014;31:1-29. [16] Turk DC, Okifuji A. Psychological aspects of pain. In: Warfield CA, Bajwa ZH, editors. Principles and practice of pain medicine. 2nd ed. New York: McGraw-Hill; 2004. p. 139-47. [17] Leeuw M, Goossens ME, Linton SJ, Crombez G, Boersma K, Vlaeyen JW. The fear-avoidance model of musculoskeletal pain: current state of scientific evidence. J Behav Med 2007;30:77-94.
Case report
A case of scrotal pain associated with genitofemoral nerve injury following cystectomy Tetsuya Sakai MD, PhD ⁎, Hiroaki Murata MD, PhD, Tetsuya Hara MD, PhD Department of Anesthesiology, Nagasaki University School of Medicine Received 29 December 2014; revised 27 January 2016; accepted 16 February 2016
Keywords: Genitofemoral nerve; Pelvic lymphadenectomy and pregabalin; Postoperative neuropathy; Radical cystectomy
Abstract The genitofemoral neuropathy is one of the most common causes of groin pain after surgery. Especially, the groin pain induced by genitofemoral nerve injury during herniorrhaphy is a well-known complication. In contrast, much attention is not paid for groin pain induced by genitofemoral nerve injury after pelvic surgery, and there have been few reports in males, although it has been reported in females. We report a 59-year-old male patient who suffered from scrotal pain caused by presumed genitofemoral nerve injury during radical cystectomy and bilateral pelvic lymphadenectomy for bladder cancer. The surgical procedure was performed in a supine position under general anesthesia, without epidural anesthesia. Postoperatively, he complained of burning and lancinating pain in bilateral scrotal area. Abnormal findings were not evident using computed tomography and ultrasonography of the pelvis, including the scrotum and testicles. He had severe allodynia of the ventral scrotum and bilateral ventromedial thigh region, with absence of cremasteric reflex. We speculated that his pain might have been surgery-induced genitofemoral neuropathy, which was caused by nerve injury during lymphadenectomy near the external iliac vessels. His scrotal pain and allodynia following the cystectomy were partially and gradually relieved after administering pregabalin, further supporting the contention that his scrotal pain was a surgery-induced neuropathy. © 2016 Elsevier Inc. All rights reserved.
1. Introduction The genitofemoral neuropathy is one of the most common causes of groin pain encountered in clinical practice [1–4]. The genitofemoral neuropathy is basically caused by the genitofemoral nerve injury anywhere along its path, including iatrogenic direct trauma to the nerve, as well as damage during inguinal herniorrhaphy [3], varicocelectomy [4], pelvic surgery [1,2], and sympathetic nerve block procedure [5], although it may rarely occur idiopathically [6,7]. Especially, the groin pain induced by genitofemoral nerve injury during herniorrhaphy is a well-known complication. This pain is lancinating and radiates ⁎ Corresponding author at: Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Tel.: +81 95 819 7370; fax: +81 95 819 7373. E-mail address: [email protected] (T. Sakai). http://dx.doi.org/10.1016/j.jclinane.2016.02.022 0952-8180/© 2016 Elsevier Inc. All rights reserved.
to the groin area, including the ventral scrotum in males [3,8]. In contrast, much attention is not paid for groin pain induced by genitofemoral nerve injury after pelvic surgery in males and there have been few reports, although it has been reported in females [1]. We report such a patient who suffered from scrotal pain caused by presumed genitofemoral neuropathy following cystectomy. We took an opportunity of this report to review the causes, circumstances, and diagnosis about postoperative genitofemoral neuropathy.
2. Case report Three months ago, a 59-year-old (body weight, 69 kg; height, 169 cm) man underwent radical cystectomy and bilateral pelvic lymphadenectomy for bladder cancer. He had no
Neuropathic scrotal pain following cystectomy
151
Quadratus lumborum muscle
Genitofemoral nerve
Psoas muscle Presumed genitofemoral nerve injury point External iliac vessel
Ilioinguinal nerve
Genital branch of genitofemoral nerve
Femoral branch of genitofemoral nerve
Fig. 1
Courses of the genitofemoral and ilioinguinal nerves and the external iliac vessels.
medical history, including diabetes mellitus and neuropathy, and result of neurologic examination was normal at admission. The surgical procedure was performed with the patient in a supine position under general anesthesia, without any peripheral/ central nerve block. The duration of the surgery was 8 hours. On postoperative day 1, he complained of burning and lancinating pain in bilateral scrotal area. Abnormal findings were not observed using computed tomography and ultrasonography of the abdomen and pelvis, including the scrotum, testicles, prostate, and epididymis. Results of lumbar spine magnetic resonance imaging and brain computed tomography were equally unremarkable. His pain with hyperalgesia was exacerbated by wearing underwear and walking and hip extension. He was referred to our clinic 2 months after surgery because the prescribed anti-inflammatory analgesics were ineffective. The intensity of his scrotal pain was 10 (on a 010 numerical rating scale), and a neurologic examination showed severe allodynia with hyperalgesia and dysesthesia in bilateral ventral scrotal and ventromedial thigh regions, with a right-side dominance. Tapping the skin immediately proximal to the pubic tubercle on a line linking the anterior superior iliac spine to the pubic symphysis elicited the scrotal pain. The bilateral cremasteric reflex was absent. The patient did not have any motor weakness, dysuria, and dyschezia. On the basis of his sign and symptom, we speculated that his pain might have been surgery-induced genitofemoral neuropathy, which
was caused by nerve injury during lymphadenectomy near the external iliac vessels, resulting in the described scrotal pain (Fig. 1). Initially, we prescribed pregabalin (75 mg/d), and within a week, his scrotal pain intensity had decreased to 5 and he was very satisfied with the analgesic effect of pregabalin. The patient continued taking flexible-dose pregabalin based on tolerability (25-150 mg/d taken once or twice daily) for 7 months; at that time, his pain and allodynia were greatly diminished, and then pregabalin was stopped (Fig. 2).
3. Discussion In this case, the patient's scrotal pain is likely to have been induced by genitofemoral nerve injury during lymphadenectomy near the external iliac vessels. The diagnosis was assessed based on his painful area that corresponded to the domain innervated by the genital branch of genitofemoral nerve, the absence of cremasteric reflex, and the normal image findings at central/spinal level. The genitofemoral nerve originates from L1 and L2 and emerges from the psoas muscle. It runs along the ventral surface of the psoas muscle and divides into the genital and femoral branches. The genital branch crosses over to the external iliac vessels in the pelvis and then supplies motor fiber to the cremasteric muscle and sensory fibers to the skin of the ventral scrotum and upper inner thighs, with a dominance of scrotum [9–12].
NRS
Pregabalin (mg/day)
10
150
100 5 50
0
0 0
10
20
30
Time (weeks) after starting pregabalin therapy
Fig. 2
Time course of numerical rating scale (NRS) of scrotal pain and the dose of pregabalin. Open circle, NRS; closed triangle, pregabalin dose.
152 The groin area receives sensory innervation not only from genitofemoral but also from the ilioinguinal nerves [9,10]. Given the area of the pain and allodynia described in the present case, we had to diagnose which nerve of ilioinguinal or genitofemoral might have been injured during the surgery. The ilioinguinal nerve also innervates the skin of the ventral scrotum and upper inner thighs same as the genitofemoral nerve, and these nerves sometimes overlap each other, making discrimination between the nerves difficult [9,10]. The ilioinguinal and genitofemoral nerves are known to be easily injured intraoperatively at the level of inguinal canal, lower abdomen, and retroperitoneum. Commonly, nerve injuries at the levels of inguinal canal or lower abdomen are observed after herniorrhaphy [3] or extended transverse incisions, such as Pfannenstiel incisions, respectively [8]. The present patient underwent surgery involving the abdominal median section. Although the ilioinguinal nerve also emerges from the lateral border of the psoas muscle, it passes obliquely across the quadratus lumborum [11]. Because the quadratus lumborum is located lateral and dorsal to the psoas muscle, the ilioinguinal nerve is not more likely to be injured than the genitofemoral nerve at the level of retroperitoneum. Large pelvic surgeries, with or without radical lymphadenectomies, are known to result in injury to the nerves coursing through the pelvis, especially when lymphadenectomy is performed [1,2]. In addition, the cremasteric reflex was absent in the patient. Therefore, we speculate that the genital branch of genitofemoral nerve was affected during lymphadenectomy near the external iliac vessels at the level of retroperitoneum. Some diagnostic approaches, including selective nerve block and electromyography, are suggested to distinguish which nerve of ilioinguinal or genitofemoral nerve is damaged [8,12]. We also proposed to the patient to undergo these approaches for diagnosis. However, the patient was satisfied with the oral medication and refused additional diagnostic tests. Among antiepileptic drugs (gabapentin and pregabalin) recommended as first-line treatment for neuropathic pain, pregabalin was chosen in accordance with our institution practice. Neuropathic pain has been defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system [13,14]. In the present case, pregabalin partially and gradually improved the patient's postcystectomy scrotal pain 1 week after administration, also suggesting that the scrotal pain described in the present case report was surgery-induced neuropathic pain. In addition, pregabalin has sedative and antianxious effects [14,15]. Negative psychic symptoms, especially anxiety, are thought to be causes to exacerbate a pain. We speculate that pregabalin improved his
T. Sakai et al. anxiety directly, which may have contributed to alleviate his pain indirectly [16,17]. In conclusion, our report shows that postoperative scrotal pain caused by the genitofemoral neuropathy may occur following radical cystectomy, with lymphadenectomy near the external iliac vessels.
References [1] Cardosi RJ, Cox CS, Hoffman MS. Postoperative neuropathies after major pelvic surgery. Obstet Gynecol 2002;100:204. [2] Irvin W, Andersen W, Taylor P, Rice L. Minimizing the risk of neurologic injury in gynecologic surgery. Obstet Gynecol 2004;103:374-82. [3] Ducic I, Dellon AL. Testicular pain after inguinal hernia repair: an approach to resection of the genital branch of genitofemoral nerve. J Am Coll Surg 2004;198:181-4. [4] Muensterer OJ. Genitofemoral nerve injury after laparoscopic varicocelectomy in adolescents. J Urol 2008;180:2155-8. [5] Sayson SC, Ramamurthy S, Hoffman J. Incidence of genitofemoral nerve block during lumbar sympathetic block: comparison of two lumbar injection sites. Reg Anesth 1997;22:569-74. [6] Rischbieth RH. Genito-femoral neuropathy. Clin Exp Neurol 1986;22: 145-7. [7] O'Brien MD. Genitofemoral neuropathy. Br Med J 1979;21:1052. [8] ter Meulen BC, Peters EW, Wijsmuller A, Kropman RF, Mosch A, Tavy DL. Acute scrotal pain from idiopathic ilioinguinal neuropathy: diagnosis and treatment with EMG-guided nerve block. Clin Neurol Neurosurg 2007;109:535-7. [9] Sasaoka N, Kawaguchi M, Yoshitani K, Kato H, Suzuki A, Furuya H. Evaluation of genitofemoral nerve block, in addition to ilioinguinal and iliohypogastric nerve block, during inguinal hernia repair in children. Br J Anaesth 2005;94:243-6. [10] Rab M, Ebmer And J, Dellon AL. Anatomic variability of the ilioinguinal and genitofemoral nerve: implications for the treatment of groin pain. Plast Reconstr Surg 2001;108:1618-23. [11] Mirilas P, Skandalakis JE. Surgical anatomy of the retroperitoneal spaces, part IV: retroperitoneal nerves. Am Surg 2010;76:253-62. [12] Cesmebasi A, Yadav A, Gielecki J, Tubbs RS, Loukas M. Genitofemoral neuralgia: a review. Clin Anat 2015;28:128-35. [13] O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med 2009;122:S22-32. [14] Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85:S3-14. [15] Darbà J, Kaskens L, Pérez C, Álvarez E, Navarro-Artieda R, SicrasMainar A. Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. Adv Ther 2014;31:1-29. [16] Turk DC, Okifuji A. Psychological aspects of pain. In: Warfield CA, Bajwa ZH, editors. Principles and practice of pain medicine. 2nd ed. New York: McGraw-Hill; 2004. p. 139-47. [17] Leeuw M, Goossens ME, Linton SJ, Crombez G, Boersma K, Vlaeyen JW. The fear-avoidance model of musculoskeletal pain: current state of scientific evidence. J Behav Med 2007;30:77-94.