Somatosensory Neuropathic Pain followingOrthopaedic Surgery
Deepak SHARAN[1] MBBS, MS Ortho, DNB Ortho, M Sc Orthopaedic Engineering, Dip. Orthopaedic and Rehabilitation Technology, CSTP®
Chronic pain is reported more frequently among surgical than non-surgical patients (Johansen A, et al., 2012).
A working definition (Macrae WA, 2008; Werner MU and Kongsgaard UE, 2014) of Chronic PostSurgical Pain (CPSP) is as follows:
Pain persisting at least 3 months after surgery (various authors propose thresholds of duration from 2 to 6 months);
Pain not present before surgery or that has different characteristics or increased intensity from preoperative pain;
Pain is localised to the surgical site or a referred area;
Other possible causes of the pain are excluded (e.g., cancer recurrence, infection).
The reported incidence of CPSP for all types of surgery is approximately 30% (Martinez et al., 2013). Hence, CPSP has become a health priority and has been included in the recent version of the International Classification of Diseases, ICD-11.
Neuropathic pain (NP) can be one of the components of acute post-surgical pain. NP is often under-recognised and is challenging to treat, with more than 50% patients experiencing only partial or no pain relief (Raja & Wallace, 2015). The prevalence of NP varies between 6 and 69%, according to the type of surgery (Martinez et al., 2013) and the screening instrument used to identify NP (Haroutiunian et al., 2013).). The prevalence of acute NP in 300 patients undergoing various types of cancer surgeries was 10% (Jain et al., 2014). A study in 170 subjects reported a prevalence of acute NP of 7-8% after surgery. The risk factors of NP development were the female gender and anxiety before surgical procedure (Brogienė et al., 2016). Acute NP often leads to development of chronic NP. Neuropathic CPSP contributes to quality of life impairment, leading to a greater use of health care facilities (Attal et al., 2011).
Intraoperative nerve damage and the extent of surgery are important (but not the sole) risk factors for the development of neuropathic CPSP (Kehlet et al., 2006; Katz & Seltzer, 2009). Nerve injury is associated with numerous molecular and cellular changes including neuroimmune interaction causing increased excitability of the primary afferent neurons (Marchand et al., 2005; Austin et al., 2010). Sometimes, the severed afferent fibres do not heal, regenerate, or undergo apoptosis, but instead start to produce ectopic firing (firing not from the normal distal end of the axon, but from any other part such as a neuroma), a phenomenon often seen in phantom pain and stump pain. The pain sensitisation is then propagated to the spinal cord along with an increased synaptic transmission and plasticity up to the spinal cord and the brain (Latremoliere & Woolf, 2009). However, many patients with peripheral nerve injuries do not develop CPSP. For instance, development of chronic NP after traumatic nerve injury occurs in less than 5% of individuals (Sunderland, 1993) and this variability is perhaps a consequence of recruiting endogenous pain inhibitory systems arising from the central nervous system (Yarnitsky et al., 2008).
Surgery for sarcoma often causes nerve damage as the surgical dissection often violates the internervous plane. Out of 144 subjects studied, 36 patients (25%) had NP. Surgery of the pelvis and multiple surgeries were predictive of neuropathic CPSP (Park et al., 2018).
NP is common after spinal surgery (the so-called failed back surgery syndrome). Potential causes include residual spinal stenosis, instability, a synovial cyst, a pseudomeningocele, internal disc disruption, epidural fibrosis, facet syndrome, sacroiliac joint syndrome, Complex Regional Pain Syndrome (CRPS), arachnoiditis and psychological problems (Rigoard P, et al., 2015).
A study on a cohort of 271 subjects who underwent open reduction and internal fixation of unstable ankle fractures found persistent NP symptoms in 61 (23%). In univariate analysis, NP was associated with age, hypertension, a thyroid disorder, lower back pain, fracture dislocations, and late complications such as non-union, posttraumatic arthritis, or osteochondral injury. In multivariate analysis, an age between 40 and 60 years was found to be a significant predictor of NP (Rbia et al., 2017).
CPSP is common 1 year after ankle and wrist fracture surgery. A study of 328 subjects, reported that 18.9% experienced CPSP, 42.8% reported symptoms suggestive of NP, and 4% fulfilled the diagnostic patient-reported research criteria for CRPS (Friesgaard et al., 2016).
The development of CRPS following orthopaedic surgery complicates post-surgical management and has profound clinical consequences. Early diagnosis is crucial to prevent the sequelae such as swelling, atrophy, osteoporosis, pseudo-arthrosis, joint stiffness and tendon adhesions. The incidence of CRPS following shoulder, distal radius, carpal tunnel and Dupuytren’s contracture surgery is estimated to be between 0.9 and 11%, 22 to 39%, 2 to 5% and 4.5 to 40%, respectively (Goh et al., 2017). The incidence of CRPS following surgery for tibial fractures was 31%, including 33.3% of patients treated with intramedullary nailing, 28.6% of patients treated with nails and screws and 28.6% of patients treated with external fixation (Sarangi et al., 1993). A study on elective ankle and foot surgery in 390 patients found the overall incidence of CRPS to be 4.4%; 3.6% for CRPS type I and 1.8% for CRPS type II (Rewhorn et al., 2014).
A cohort study including 1292 patients reported a 48% prevalence of CPSP 3 months after all types of orthopaedic and trauma surgery. NP was present in 43% of patients suffering from CPSP, and was associated with an increase in analgesic consumption, sleep disturbance and sick leave. Elbow epicondylitis debridement, meniscectomy, amputation and neurolysis were the types of surgery with the highest prevalence of NP (Fuzier et al., 2015).
After Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA), the reported prevalence of CPSP varies between 5 and 44% (Buvanendran et al., 2010; Wylde et al., 2011). The prevalence of chronic NP after TKA varies between 8% and 13% at 3 and 6 months and the mean reported amount of time that elapses before NP appears after TKA is 16 months (Harden et al., 2003; Buvanendran et al., 2010; Phillips et al., 2014).
In the EDONIS study in France, the prevalence for CPSP was 51 and 48.5%, 3 and 6 months after knee arthroscopy, respectively (Duale et al., 2014). NP (as assessed by Douleur Neuropathique 4 DN4) was found in 11% of cases. CPSP was found in 35% of patients three months after autogenous iliac crest bone graft, of which 23% had NP (Martinez et al., 2012).
Another study on subjects who underwent surgery for intramedullary spinal cord tumours found that NP varied depending on the tumour location, tumour type, severity of paralysis, and the location of the pain (i.e., at and/or below the level of the tumor). Subjects with hemangioblastoma were likely to develop NP at the level of the tumour after surgery, possibly involving the dorsal horn of spinal cord. Subjects other than those with hemangioblastoma who showed incomplete paralysis postoperatively and NP below the level of the tumour, involvement of the spinothalamic tract was likely (Nakamura et al., 2012).
Neuropathic CPSP has been reported among children with Cerebral Palsy (CP) following Single Event Multilevel Lever Arm Restoration Anti Spasticity Surgery (SEMLARASS) – a combination of myofascial surgery and osteotomies. A total of 81 children out of 500 studied (mean age of 13.7 years) were diagnosed to have NP (16.2% of the total). The regions involved were plantar aspect of foot (45.7%), lateral aspect of thigh (30.9%), and lateral aspect of tibia (23.5%). Three children were diagnosed to have CRPS type I. The risk factors for NP included older age (> 8 years), severe CP (GMFCS levels 4 and 5), longer duration of plaster immobilisation (> 6 weeks), previous chemodenervation using Phenol injections and neurosurgical procedures such a selective motor fasciculotomy. 72 children recovered completely following the somatosensory rehabilitation, while 7 children with foot drop and 2 children with dysesthesia following phenol injections recovered partially (Sharan et al., 2016).
Orthopaedic surgery is usually performed to relieve pain. This fact complicates the assessment of pain persisting after surgery. For example, 1 year after carpal tunnel decompression surgery, 36% of subjects reported pain in the wrist and/or hand on the operated side; pain different from the preoperative pain was reported by 22% of patients and pain similar to the preoperative pain by 12% of subjects (Belze et al., 2012).
The prevalence of NP was 50% after thoracic surgery and a higher total score on the PainDETECT scale correlated with more intense pain (Steegers et al., 2008)
A correlation was found between a positive DN4 and the risk of developing a mild to severe CPSP (Duale et al., 2014). CPSP intensity is likely to increase with time in case of positive DN4 (Duale et al., 2014).
A quantitative and qualitative assessment of NP early in the postoperative period could permit the initiation of adequate treatment, thus limiting the risk of development of CPSP and decreasing the related consequences (adverse drug reactions, costs for society due to medications and sick leave) (Fuzier et al., 2015).
A nerve injury-induced neuropathic pain probability grading system has been proposed to identify surgeries at high risk of developing NP (Haroutiunian et al., 2013).
Prediction of CPSP might theoretically allow pre-emptive targeting of individuals at risk:
Clinical factors predict approximately 70% of CPSP risk (Montes et al., 2016): type of surgery, age, physical and mental health, and preoperative pain (at the surgical site or other location);
A prospective risk-factor analysis identified five key predictive factors: emotional overload/overstrain, preoperative pain in the area to be operated upon, other chronic preoperative pain (e.g., headache), acute postoperative pain, and comorbid stress symptoms such as tremulousness, anxiety, rumination, magnification, helplessness or disturbed sleep (Althaus et al., 2012);
Preoperative use of opioid increases the risk of CPSP with an RR of 2.0 (95 percent confidence interval, 1.2-3.3) (VanDenKerkhof et al., 2012);
Postoperative pain is an important determinant of the development of CPSP, particularly the duration of severe pain after surgery, i.e., the amount of time spent in severe unrelieved pain rather than, for example, a single peak pain intensity rating (Fletcher D, et al., 2015);
Early NP might predict neuropathic CPSP (Martinez et al., 2012).
Use of minimally invasive and nerve-sparing incisional techniques to avoid partial nerve lesion decreases the risk of NP (Martinez et al., 2012). Regional anaesthesia (e.g., epidural analgesia or paravertebral block) and Ketamine infused perioperatively may reduce the risk of CPSP in some individuals.
If NP is diagnosed in the early postoperative period, Gabapentinoids and tricyclic antidepressants are recommended for the treatment (Martinez et al., 2013). Perioperative pregabalin administration reduces the incidence of chronic NP after major orthopaedic surgery, like TKA (Buvanendran et al., 2010). This positive effect was not found after ankle surgery (Yadeau et al., 2012).
The somatosensory rehabilitation method is recommended for the detection, classification and treatment of NP following orthopaedic surgery (Spicher et al., 2016).
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Rewhorn MJ, Leung AH, Gillespie A, Moir JS, Miller R. Incidence of complex regional pain syndrome after foot and ankle surgery. J Foot Ankle Surg. 2014;53(3):256-8.
Rigoard P, Blond S, David R, Mertens P. Pathophysiological characterisation of back pain generators in failed back surgery syndrome (part B). Neurochirurgie 2015;61 Suppl 1:S35-44.
Sarangi PP, Ward AJ, Smith EJ, Staddon GE, Atkins RM. Algodystrophy and osteoporosis after tibial fractures. J Bone Joint Surg. 1993;75(3):450-2.
Sharan D, Rajkumar JS, Balakrishnan R. Neuropathic pain following a single event multilevel lever arm restoration antispasticity surgery for children with cerebral palsy. Jain P, Padole D, Bakshi S. Prevalence of acute neuropathic pain after cancer surgery: A prospective study. Indian Journal of Anaesthesia 2014; 58(1): 36-42.
Johansen A, Romundstad L, Nielsen CS, Schirmer H, Stubhaug A. Persistent postsurgical pain in a general population: prevalence and predictors in the Tromso study. Pain 2012;153:1390-6.
Katz J, Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert Rev Neurother. 2009 May;9(5):723-44.
Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006;367:1618–25.
Latremoliere A, Woolf CJ. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J Pain 2009; 10:895–926.
Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci 2005; 6:521–32.
Martinez V, Ben Ammar S, Judet T, Bouhassira D, Chauvin M, Fletcher D. Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model. Pain 2012;153:1478–83.
Martinez V, Baudic S, Fletcher D. Chronic postsurgical pain. Ann Fr Anesth Reanim 2013;32:422–35.
Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth 2008;101:77–86.
Montes A, Roca G, Sabate S, Lao JI, Navarro A, Cantillo J, Canet J, Group GS. Genetic and clinical factors associated with chronic postsurgical pain after hernia repair, hysterectomy, and thoracotomy: a two-year multicenter cohort study. Anesthesiology 2015;122:112341.
Nakamura M, Tsuji O, Iwanami A, Tsuji T, Ishii K, Toyama Y, Chiba K, Matsumoto M. Central neuropathic pain after surgical resection in patients with spinal intramedullary tumor. J Orthop Sci. 2012 Jul;17(4):352-7.
Park JW, Kim HS, Yun JY, Han I. Neuropathic pain after sarcoma surgery: Prevalence and predisposing factors. Medicine (Baltimore). 2018 May;97(21):e10852.
Phillips JR, Hopwood B, Arthur C, Stroud R, Toms AD. The natural history of pain and neuropathic pain after knee replacement: a prospective cohort study of the point prevalence of pain and neuropathic pain to a minimum three-year follow-up. Bone Joint J 2014;96-B(09):1227-1233.
Raja SN, Wallace M. Neurostimulation for Neuropathic Pain: Outcomes and New Paradigms. Pain: Clin Updates 2015;23(5):1-8.
Rbia N, van der Vlies CH, Cleffken BI, Selles RW, Hovius SER, Nijhuis THJ. High prevalence of chronic pain with neuropathic characteristics after open reduction and internal fixation of ankle fractures. Foot Ankle Int. 2017 Sep;38(9):987-996.
Rewhorn MJ, Leung AH, Gillespie A, Moir JS, Miller R. Incidence of complex regional pain syndrome after foot and ankle surgery. J Foot Ankle Surg. 2014;53(3):256-8.
Rigoard P, Blond S, David R, Mertens P. Pathophysiological characterisation of back pain generators in failed back surgery syndrome (part B). Neurochirurgie 2015;61 Suppl 1:S35-44.
Sarangi PP, Ward AJ, Smith EJ, Staddon GE, Atkins RM. Algodystrophy and osteoporosis after tibial fractures. J Bone Joint Surg. 1993;75(3):450-2.
Sharan D, Rajkumar JS, Balakrishnan R. Neuropathic pain following a single event multilevel lever arm restoration antispasticity surgery for children with cerebral palsy.
[1] Consultant in Orthopaedic Surgery and Rehabilitation, RECOUP Neuromusculoskeletal Rehabilitation Centre, Bengaluru, India. E-mail: drdeepaksharan@yahoo.com
