Abstract
The transition from a healthy to a persistent severe pain state following otherwise successful elective surgery is a feared complication. Groin hernia repair, previously considered minor surgery, is a standard surgical procedure annually performed on 2,000 individuals per one million residents. A trajectory into persistent severe pain is, unfortunately, seen in 2–4%, severely impeding physical and psychosocial daily functions.
Preface
Groin hernia repair is a high-volume procedure with an estimated 15 million repairs worldwide each year [1, 2]. The pathophysiology behind the occurrence of persistent severe pain after groin hernia repair has been investigated by somatosensory testing in several studies [3, 4]. Somatosensory testing is a standardized activation of the sensory system by application of calibrated physiological stimuli, with an assessment of the graded evoked psychophysical responses [5]. Intriguingly, a concerted effort to synthesize these results with clinical and histopathological findings has not been made. Thus, the aims of the lecture are two-fold: first, to give an overview of the prevalence and the pathophysiology behind persistent severe pain after groin hernia repair, and second, to integrate the somatosensory testing data into a comprehensive pathophysiological model for persistent severe post-surgical pain. Such efforts may improve contemporary guidelines for pain management.
Surgery
Groin hernia repair is an interesting surgical pathophysiological model to study. The repair, although previously considered belonging to “minor” surgeries, qualifies as a rather complex procedure performed in a territory with a high density of nerve fibers and a rich vascular supply, accommodating essential functions for locomotion, proprioception and reproduction. The high-volume procedure, is performed by standardized techniques, using open (anterior) or laparoscopic (total extraperitoneal (TEP), transabdominal preperitoneal (TAPP) or robotic TAPP) approaches. In adults, the defect in the abdominal wall is repaired by a mesh implant made of lightweight or heavyweight polypropylene, but also absorbable meshes (biological or synthetic absorbable) are available [6]. Mesh-induced inflammation is central to the development of persistent pain (see below).
Prevalence of persistent pain
The surgical technique and the mesh type may affect the development of persistent pain. While study differences across techniques and mesh types are surprisingly small, minimally invasive repair appears associated with a reduced risk of postoperative hematoma, wound infection, earlier return to work/daily activities, and a decrease in the prevalence of persistent pain. Nevertheless, high-volume studies with longer follow-ups are still needed to avoid confounding factors shrouding the evidence [1].
From a scholar’s point of view, the intensity of persistent pain and the pain-related impact on physical, psychological, and socioeconomic functions are important to characterize [7], [8], [9]. The prevalence of persistent severe pain after groin hernia repair ranges in the literature from 1–15%, depending on the strictness of evaluation criteria [10, 11], potentially affecting 300.000 individuals annually worldwide.
Pain trajectories
The pain trajectory from primary surgery to a persistent severe pain state has been investigated by examinator-guided individual interviews (n=95) [12]. Several interesting and clinically relevant findings were seen. First, two main categories of trajectories were delineated. One category of trajectory was a continuation of the acute post-surgical high-intensity pain (47% [48/95]) (Figure 1), (A), while the other category belonged to a delayed onset of persistent severe pain (29% [28/95]); (B). Second, a “phenotype shift” (C), only observable during a longitudinally designed study, was observed, meaning that the number of individuals with persistent pain at a given time point often is underestimated, and the likelihood of experiencing a successive decrease in pain intensity, without re-surgical intervention, is high [9, 12]. The “phenotype shift” has been corroborated in longitudinal cohort studies [13], including various other surgical procedures [14], [15], [16].
![Figure 1:
Illustration of two categories of pain trajectories after groin hernia surgery [12].
(A) illustrates the continuation of the acute post-surgical high-intensity pain with a late reduction in pain intensity. (B) illustrates a delayed onset of persistent pain after a post-surgical period of no pain. (C) illustrates a “phenotype shift”: high-intensity persistent pain at the 6-month time point (blue curve) but no pain at the 2-year time point vis-á-vis no pain at the 6-month trajectory (red curve), transitioning to high-intensity pain after a delayed onset.](/document/doi/10.1515/sjpain-2022-0103/asset/graphic/j_sjpain-2022-0103_fig_002.jpg)
Illustration of two categories of pain trajectories after groin hernia surgery [12].
(A) illustrates the continuation of the acute post-surgical high-intensity pain with a late reduction in pain intensity. (B) illustrates a delayed onset of persistent pain after a post-surgical period of no pain. (C) illustrates a “phenotype shift”: high-intensity persistent pain at the 6-month time point (blue curve) but no pain at the 2-year time point vis-á-vis no pain at the 6-month trajectory (red curve), transitioning to high-intensity pain after a delayed onset.
Mesh pathology
Key triggers in the pathophysiologic events relate to the mesh implant procedure, not only observable in groin hernia repair but also seen in other surgical procedures, e.g., breast implants, vascular grafts, and joint prosthetic material [17]. Nerve injury caused by the surgical dissection per se or the fixation of the mesh (sutures, tacks) may lead to nerve damage and delayed onset of neuropathic pain. Further, the mesh implant is vulnerable to dehiscence, dislocation, induration, invasion of adjacent structures, or shrinkage leading to a reduction of the mesh area by 20–90% [18, 19]. The development of an inflammatory meshoma may also potentially lead to painful irritation of the surgically altered tissues in the groin [17, 20, 21].
Histopathological studies in explanted meshes have demonstrated chronic foreign body giant-cell granulomas with immunoinflammatory reactions and neo-innervation by nerve fibers [6, 18]. Interestingly, a significantly higher nerve fiber density was observed in explants obtained due to re-surgery for persistent pain than for non-pain hernia recurrence [18]. However, the clinical significance of these findings has recently been questioned in a high-volume study [17].
In the meshoma, the fibrosis progression may impinge upon or compress the spermatic cord leading to movement-related pain and dysejaculation [22]. Additionally, peripheral nerves, e.g., the ilioinguinal nerve and the genital branch of the genitofemoral nerve, may become embedded in the meshoma or the scar tissue resulting in functional and structural nerve damage and the formation of neuromas.
Somatosensory physiology
Sensory cutaneous stimulation in the groin area generates neural responses from nerve fiber endings located in the skin and deeper tissues. While the responses to superficial punctate (<1 mm2) mechanical as well as thermal stimuli are generated from receptors located in the epidermis and upper dermis, the stimulation by blunt pressure (1 cm2) algometry activates pain receptors in the deeper connective tissue layers. These fascial tissues are essential in the physiology of deep pain [23]. Recently, detailed studies of fascial innervation have been published, indicating that specific neural networks reside in the superficial and deep fasciae and that these networks are implicated in pain and proprioceptive responses [24, 25].
Somatosensory pathophysiology
This part focuses primarily on findings related to anterior open mesh repairs since detailed somatosensory studies on laparoscopic procedures are scarce [26].
Previous studies have demonstrated a significant decrease in intraepidermal nerve fiber intensity (IENFD), comparing the surgical groin with the non-surgical groin [27, 28]. The loss of nerve fibers translates into an increase in punctate mechanical and thermal detection and pain thresholds, i.e., hypoesthesia and hypoalgesia, respectively.
The point of maximum palpatory evoked pain corresponds to the superficial inguinal ring, i.e., the outer opening of the inguinal canal in the abdominal wall accommodating the spermatic cord, ilioinguinal nerve, the genital branch of the genitofemoral nerve, and the vascular supply to the testicles [9]. Blunt pressure algometry, with more than 100 times higher stimulation area than punctate stimuli, when applied at the superficial inguinal ring, compresses the deeper situated structures exiting from the inguinal canal as well as the covering meshoma. Several studies have demonstrated significantly decreased pain thresholds in the surgical groin, corresponding to a gain in nociceptive function, i.e., hyperalgesia.
To sum up, the data indicate that the primary groin hernia repair causes a partial “deafferentation” of the superficial structures but also induces the development of a “pain generator” situated in the deeper fascial structures.
Two studies have specifically addressed the “pain generator” issue [29, 30]. Both studies were double-blind, crossover RCTs using an ultrasound-guided block. The first study targeted the iliohypogastric and ilioinguinal nerves at the level of the anterior superior iliac spine (n=12) [29]. However, no effect on the severe persistent pain was seen, indicating that a block of the genitofemoral nerve (innervating the groin “downstream”) likely was necessary to obtain pain relief. In the second study (n=14) [30], using a block at the tender point situated in the superficial inguinal ring, the median reduction in pain was 63% compared to 36% after placebo (p=0.003) [30]. The pain intensities were assessed during rest, movement, and algometry. The pain relief was, however, short-lasting. The study indicated that peripheral afferent input from the tender point area is important for the maintenance of spontaneous and evoked pain in persistent severe pain after groin hernia repair.
Several studies have indicated that re-surgery, including meshectomy and selective or triple neurectomy, may offer significant pain relief and improve functional scores compared to control cohorts [31, 32]. Recent, unpublished observations[1] by the present authors indicate that re-surgery, i.e., meshectomy and selective neurectomy, is followed by additional decreases in punctate mechanical and thermal thresholds and, remarkably, significant increases in blunt pressure algometry ratings. The hypoalgesic effects of re-surgery corroborate that meshectomy with an adjuvant neurectomy may partially disable the “pain generator”.
Conclusions
Meshoma-related events are essential components in the pathophysiology of persistent severe pain after groin hernia repair; the events indicate a primary inflammatory substrate for the pain. However, neuropathic components are ubiquitously present.
Acknowledgements
The authors extend special and heartfelt thanks to all participating study subjects since 2002.
-
Research funding: Only departmental resources.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
References
1. Aiolfi, A, Cavalli, M, Ferraro, SD, Manfredini, L, Bonitta, G, Bruni, PG, et al.. Treatment of inguinal hernia: systematic review and updated network meta-analysis of randomized controlled trials. Ann Surg 2021;274:954–61. https://doi.org/10.1097/sla.0000000000004735.Search in Google Scholar PubMed
2. International, GH. Guidelines for groin hernia management. Hernia 2018;22:1–165. https://doi.org/10.1007/s10029-017-1668-x.Search in Google Scholar PubMed PubMed Central
3. Mikkelsen, T, Werner, MU, Lassen, B, Kehlet, H. Pain and sensory dysfunction 6 to 12 months after inguinal herniotomy. Anesth Analg 2004;99:146–51. https://doi.org/10.1213/01.ane.0000115147.14626.c5.Search in Google Scholar PubMed
4. Aasvang, EK, Gmaehle, E, Hansen, JB, Gmaehle, B, Forman, JL, Schwarz, J, et al.. Predictive risk factors for persistent postherniotomy pain. Anesthesiology 2010;112:957–69. https://doi.org/10.1097/aln.0b013e3181d31ff8.Search in Google Scholar PubMed
5. Mücke, M, Cuhls, H, Radbruch, L, Baron, R, Maier, C, Tölle, T, et al.. Quantitative sensory testing (QST). English version. Schmerz. 2021;35:153–60. https://doi.org/10.1007/s00482-015-0093-2.Search in Google Scholar PubMed
6. Klinge, U, Klosterhalfen, B. Mesh implants for hernia repair: an update. Expet Rev Med Dev 2018;15:735–46. https://doi.org/10.1080/17434440.2018.1529565.Search in Google Scholar PubMed
7. Bande, D, Moltó, L, Pereira, JA, Montes, A. Chronic pain after groin hernia repair: pain characteristics and impact on quality of life. BMC Surg 2020;20:147. https://doi.org/10.1186/s12893-020-00805-9.Search in Google Scholar PubMed PubMed Central
8. Powell, R, Johnston, M, Smith, WC, King, PM, Chambers, WA, Krukowski, Z, et al.. Psychological risk factors for chronic post-surgical pain after inguinal hernia repair surgery: a prospective cohort study. Eur J Pain 2012;16:600–10. https://doi.org/10.1016/j.ejpain.2011.08.010.Search in Google Scholar PubMed
9. Jensen, EK, Ringsted, TK, Bischoff, JM, Petersen, MA, Rosenberg, J, Kehlet, H, et al.. A national center for persistent severe pain after groin hernia repair: five-year prospective data. Medicine (Baltim) 2019;98:e16600. https://doi.org/10.1097/MD.0000000000016600.Search in Google Scholar PubMed PubMed Central
10. Lundstrom, KJ, Holmberg, H, Montgomery, A, Nordin, P. Patient-reported rates of chronic pain and recurrence after groin hernia repair. Br J Surg 2018;105:106–12. https://doi.org/10.1002/bjs.10652.Search in Google Scholar PubMed
11. Bright, E, Reddy, VM, Wallace, D, Garcea, G, Dennison, AR. The incidence and success of treatment for severe chronic groin pain after open, transabdominal preperitoneal, and totally extraperitoneal hernia repair. World J Surg 2010;34:692–6. https://doi.org/10.1007/s00268-010-0410-y.Search in Google Scholar PubMed
12. Jensen, EK, Bäckryd, E, Hilden, J, Werner, MU. Trajectories in severe persistent pain after groin hernia repair: a retrospective analysis. Scand J Pain 2021;21:70–80. https://doi.org/10.1515/sjpain-2020-0104.Search in Google Scholar PubMed
13. Reinpold, WM, Nehls, J, Eggert, A. Nerve management and chronic pain after open inguinal hernia repair: a prospective two phase study. Ann Surg 2011;254:163–8. https://doi.org/10.1097/SLA.0b013e31821d4a2d.Search in Google Scholar PubMed
14. Gartner, R, Jensen, MB, Nielsen, J, Ewertz, M, Kroman, N, Kehlet, H. Prevalence of and factors associated with persistent pain following breast cancer surgery. JAMA 2009;302:1985–92. https://doi.org/10.1001/jama.2009.1568.Search in Google Scholar PubMed
15. Hetmann, F, Kongsgaard, UE, Sandvik, L, Schou-Bredal, I. Prevalence and predictors of persistent post-surgical pain 12 months after thoracotomy. Acta Anaesthesiol Scand 2015;59:740–8. https://doi.org/10.1111/aas.12532.Search in Google Scholar PubMed
16. Johansen, A, Schirmer, H, Nielsen, CS, Stubhaug, A. Persistent post-surgical pain and signs of nerve injury: the tromso study. Acta Anaesthesiol Scand 2016;60:380–92. https://doi.org/10.1111/aas.12653.Search in Google Scholar PubMed
17. Fadaee, N, Mazer, L, Sharma, R, Capati, I, Balzer, B, Towfigh, S. Clinical value of hernia mesh pathology evaluation. J Am Coll Surg 2019;228:776–81. https://doi.org/10.1016/j.jamcollsurg.2019.02.038.Search in Google Scholar PubMed
18. Bendavid, R, Lou, W, Grischkan, D, Koch, A, Petersen, K, Morrison, J, et al.. A mechanism of mesh-related post-herniorrhaphy neuralgia. Hernia 2016;20:357–65. https://doi.org/10.1007/s10029-015-1436-810.1007/s10029-015-1436-8.Search in Google Scholar
19. Iakovlev, V, Koch, A, Petersen, K, Morrison, J, Grischkan, D, Oprea, V, et al.. A pathology of mesh and time: dysejaculation, sexual pain, and orchialgia resulting from polypropylene mesh erosion into the spermatic cord. Ann Surg 2018;267:569–75. https://doi.org/10.1097/sla.0000000000002134.Search in Google Scholar
20. Amid, PK. Causes, prevention, and surgical treatment of postherniorrhaphy neuropathic inguinodynia: triple neurectomy with proximal end implantation. Hernia 2004;8:343–9. https://doi.org/10.1007/s10029-004-0247-0.Search in Google Scholar PubMed
21. Reinpold, W. Risk factors of chronic pain after inguinal hernia repair: a systematic review. Innov Surg Sci 2017;2:61–8. https://doi.org/10.1515/iss-2017-0017.Search in Google Scholar PubMed PubMed Central
22. Nguyen, DK, Amid, PK, Chen, DC. Groin pain after inguinal hernia repair. Adv Surg 2016;50:203–20. https://doi.org/10.1016/j.yasu.2016.04.003.Search in Google Scholar PubMed
23. Vieira, L. Phylogenetics of the fascial system. Cureus 2020;12:e10787. https://doi.org/10.7759/cureus.10787.Search in Google Scholar PubMed PubMed Central
24. Fede, C, Porzionato, A, Petrelli, L, Fan, C, Pirri, C, Biz, C, et al.. Fascia and soft tissues innervation in the human hip and their possible role in post-surgical pain. J Orthop Res 2020;38:1646–54. https://doi.org/10.1002/jor.24665.Search in Google Scholar PubMed
25. Fede, C, Petrelli, L, Guidolin, D, Porzionato, A, Pirri, C, Fan, C, et al.. Evidence of a new hidden neural network into deep fasciae. Sci Rep 2021;11:12623. https://doi.org/10.1038/s41598-021-92194-z.Search in Google Scholar PubMed PubMed Central
26. Linderoth, G, Kehlet, H, Aasvang, EK, Werner, MU. Neurophysiological characterization of persistent pain after laparoscopic inguinal hernia repair. Hernia 2011;15:521–9. https://doi.org/10.1007/s10029-011-0815-z.Search in Google Scholar PubMed
27. Bischoff, JM, Ringsted, TK, Petersen, M, Sommer, C, Uceyler, N, Werner, MU. A capsaicin (8%) patch in the treatment of severe persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled trial. PLoS One 2014;9:e109144. https://doi.org/10.1371/journal.pone.0109144.Search in Google Scholar PubMed PubMed Central
28. Bischoff, JM, Petersen, M, Uceyler, N, Sommer, C, Kehlet, H, Werner, MU. Lidocaine patch (5%) in treatment of persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial. Anesthesiology 2013;119:1444–52. https://doi.org/10.1097/ALN.0b013e3182a2a243.Search in Google Scholar PubMed
29. Bischoff, JM, Koscielniak-Nielsen, ZJ, Kehlet, H, Werner, MU. Ultrasound-guided ilioinguinal/iliohypogastric nerve blocks for persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial. Anesth Analg 2012;114:1323–9. https://doi.org/10.1213/ane.0b013e31824d6168.Search in Google Scholar
30. Wijayasinghe, N, Ringsted, TK, Bischoff, JM, Kehlet, H, Werner, MU. The role of peripheral afferents in persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial of ultrasound-guided tender point blockade. Br J Anaesth 2016;116:829–37. https://doi.org/10.1093/bja/aew071.Search in Google Scholar PubMed PubMed Central
31. Beel, E, Berrevoet, F. Surgical treatment for chronic pain after inguinal hernia repair: a systematic literature review. Langenbecks Arch Surg. 2022;407:541–8. https://doi.org/10.1007/s00423-021-02311-9.Search in Google Scholar PubMed
32. Aasvang, EK, Kehlet, H. The effect of mesh removal and selective neurectomy on persistent postherniotomy pain. Ann Surg 2009;249:327–34. https://doi.org/10.1097/sla.0b013e31818eec49.Search in Google Scholar
© 2022 the author(s), published by De Gruyter, Berlin/Boston
This work is licensed under the Creative Commons Attribution 4.0 International License.
