1. Introduction
Neuropathic pain caused by symptomatic neuromas is an important problem following peripheral nerve injury, seriously affecting patients’ daily life. The incidence of symptomatic neuromas is estimated at approximately 3–5% of all patients involved in peripheral nerve injury [4]. The extreme spontaneous pain, allodynia, hyperalgesia and cold intolerance cause loss of function and productivity [49], resulting in high unemployment and workers’ compensation rates as well as high health care expenditures [10,20].
Neuromas are formed when nerve recovery towards the distal nerve end or target organ fails and axons sprout into the surrounding scar tissue. They consist of a deranged architecture of tangled axons, Schwann cells, endoneurial cells, and perineurial cells in a dense collagenous matrix with surrounding fibroblasts [34]. There is an up-regulation of sodium channels, adrenergic and nicotinic cholinergic receptors leading to abnormal sensitivity and spontaneous activity of injured axons [7]. As ectopic peripheral nerve input continues, changes at the spinal cord and sensory cortex level start to take place, creating a state of central sensitization [48].
Unfortunately, treatment of patients with neuroma pain is difficult. Many treatment methods have been proposed, such as injections of the nerve stump with various chemical agents, transcutaneous electrical nerve stimulation (TENS), topical lidocaine, repeated nerve blocks, desensitization techniques and adjuvant pain medication like antidepressants and anticonvulsants [15]. The treatment of disabling neuropathic pain following nerve injury is a topic that is of timeless interest to plastic- and neurosurgeons, orthopedic and general surgeons, as well as anesthesiologists and pain management teams but an entirely effective treatment method has yet to be found [54]. Although not all pain specialists are aware of this option, peripheral nerve surgery can provide a permanent effect on pain relief, as opposed to the life-long use of analgesic medication or medical devices.
Best results are usually obtained with reconstruction of the nerve using nerve grafts or neurotubes, or relocation of the painful nerve into an environment away from the original injury site and protected from mechanical, thermal, or other injury of the nerve [13], for example into bone, muscle or vein [5]. End-to-side anastomoses or nerve loops can also provide satisfactory results [54]. Despite the use of these techniques, remaining or recurrent pain is a common finding [48].
For decision making processes and patient education, it is important to know the effect of surgical treatment on different outcome domains. Since treatment failure is common, it can be important to point out patient groups that will not likely benefit from surgical treatment. Patient-specific prognostic factors, predicting insufficient pain relief after surgical neuroma treatment, can help clinicians in the process of patient selection, treatment and care. The current study was performed to evaluate the effect of surgical neuroma pain treatment on multiple important outcome domains and to find prognostic factors for insufficient pain relief, including the predictive value of commonly used diagnostic nerve blocks.
2. Methods
Between January 2006 and August 2009, we conducted a prospective follow-up study on surgically treated upper extremity neuroma pain patients. Included patients were diagnosed with neuroma specific neuropathic pain after presenting with a history of nerve injury to the upper extremity, followed by symptoms of a painful neuroma including spontaneous pain, electrical spikes or burning pain, allodynia and hyperalgesia to touch, pressure or movement [46]. Clinical examination typically showed a shooting electrical pain when tapping the injured nerve (positive Tinel's test).
In most cases, a diagnostic nerve block with 1% lidocaine was performed at the outpatient clinic, to confirm involvement of the suspected nerve in the painful sensation and to assess possible injuries to other nerves [33]. The effect of this nerve block was registered by the hand surgeon on a 0–10 pain scale. Patients that were selected by the hand surgeon to sustain a surgical procedure were sent a questionnaire approximately 2weeks prior to their operation. Follow-up questionnaires assessing primary and secondary outcomes were sent to all included patients with a follow-up period of at least 3months.
Patients were operated under general anesthesia combined with a local block or under regional anesthesia. Pre-operatively, most patients received a continuous axillary block, regulated by the anesthesiologist from the acute pain service until 24h post-operatively. Before closing the skin, a local injection with Naropin (Ropivacaïne 7.5mg/ml) was given to further reduce post-operative pain.
Pre-operatively the location of maximum pain was marked. After opening the skin, the nerve was neurolyzed from the surrounding scar tissue and the neuroma was excised. If a neuroma-in-continuity or a nerve transection with an available distal stump was present, continuity was restored. If the distal nerve was not available for repair, the proximal stump was buried into bone or muscle, preferably proximal to the site of injury. In some cases other techniques were applied such as a nerve loop or silicone sheath. Tension on the nerve was always avoided.
The lateral antebrachial cutaneous nerve (LABCN), posterior interosseous nerve (PIN), palmar branch of the median nerve (PBMN) and the anterior interosseous nerve (AIN) may have overlapping sensory innervation with the superficial branch of the radial nerve (SBRN). In case of recurrent or persistent pain, the suspected adjacent nerve involved was diagnostically blocked with 1% lidocaine and if the block showed a considerable pain reduction, a denervation was performed.
Primary outcomes were patient satisfaction (yes or no) and pain scored pre- and post-operatively on a 10cm visual analogue scale (VAS), ranging from 0 ‘no pain at all’, to 10 ‘unbearable pain’. Cut off scores for insufficient pain relief were defined as less than 3 points decrease on the VAS pain scale, or a final VAS score above 2, using the reliable change index (RCI) and clinical significant change (CSC) (data not shown) [14,23,38].
We evaluated the effect of treatment on important secondary outcome domains, including pain, physical and emotional functioning and accompanying symptoms, as proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) [52]. These secondary outcomes were assessed using validated questionnaires, including the McGill pain questionnaire (MPQ), which divides pain into sensory-discriminative, affective-motivational, and evaluative-cognitive pain [36]; the SF-36 for physical and emotional quality of life assessment [55]; the SCL-90 for assessment of psychological problems and psychopathology [45]; the Tampa scale for kinesiophobia (TSK) [18], which measures the patient's anxiety for being physically active; and the disability of arm, shoulder and hand (DASH) questionnaire, with its subscales for work and sport activities [44]. Pre- and post-operative scores were compared to each other and to normative population scores found in literature. Furthermore, we looked at different pain modalities, as described by Sood and Elliot [46], and their improvement following surgical treatment. These include ratings of spontaneous pain, pain on pressure or movement, and hypersensitivity. Pain medication usage: type and frequency were recorded both pre-operatively and after follow-up.
Prognostic factors, such as employment status, workers compensation and litigation involvement, number of previous operations and duration of pain [48], as well as other patient characteristics, such as sex, body mass index (BMI), smoking status and socio-economic status were evaluated for their effect on primary outcome. We also compared the effect of all surgical procedures performed during our study and compared the outcome for the different nerves involved in the upper extremity. The predictive value of the diagnostic nerve block performed at the outpatient clinic was determined by comparing pain scores following the nerve block with those following surgical treatment. An effective block was defined as providing a (temporary) pain score below 3.5.
Student's t-tests were used to compare two independent means and for comparing pre- and post-operative data the paired t-test was used. For paired ordinal data the Wilcoxon signed-rank test was used. Chi-square tests were performed for 2 by 2 contingency tables, when the minimum expected count per cell was at least 5. For 2 by 2 tables not meeting this criterion, Fisher's exact test was performed. For prognostic factors for the primary outcome, relative risks (RR) with 95% confidence intervals (95% CI) were calculated. Stratification was performed in case of possible confounding of results. The Mantel–Haenszel adjusted relative risk was used to provide a weighted average of the stratum-specific relative risks. To evaluate correlations between ordinal and continuous data, the non-parametric Spearman's rank correlation coefficient was used. Pearson's correlation coefficients were used for continuous data. Although multiple procedures and measurements were available for some patients, only the final operation of patients was used to compare groups, to avoid an underestimation of variability and inflation of sample size.
This study was approved by the Medical Ethics Committee of our institution (MEC-2007–094).
3. Results
From January 2006 through August 2009, pre-operative questionnaires were sent to 45 patients. Two patients did not return the questionnaire. Seven patients were excluded as no neuroma was found during surgery and only external neurolysis was performed. One patient decided to refrain from further surgical treatment. The follow up questionnaire was sent to 35 patients and returned by 34 patients, one patient did not respond. Demographics of the 34 included neuroma patients are presented in Table 1.
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Table 1: Baseline characteristics.
The study population consisted of 18 males and 16 females with an average age of 42.8years. The average duration of follow-up was 22months (range 3–37). The causes of nerve injury are presented in Table 2. There was no significant difference in outcome between traumatic and iatrogenic injuries or the type of injury (sharp, crush, avulsion).
Table 2: Causes of injury.
Primary outcomes are presented in Figs. 1 and 2. Nineteen patients (56%) were satisfied with treatment results. The mean pre-operative VAS score was 6.6 and decreased to 4.8 after follow up (p<0.001). In the satisfied patient group, the mean pain decrease was 3.0 (from 5.7 to 2.7) compared to 0.7 (from 7.8 to 7.1) in the unsatisfied group (p=0.003). Fourteen patients (41%) had a decrease of at least 3 points on the VAS for pain, or a score below 2.
Fig. 1.:
Primary outcome: patient satisfaction.
Fig. 2.:
Primary outcome: pain decrease. Paired t-test: p < 0.001. VAS, visual analogue scale for pain, range 0–10. CI, confidence interval. Primary outcome assessed after a mean follow-up period of 22 months.
Pre- and post-operative VAS, SF-36, TSK, CISS, SCL-90 and MPQ scores, as well as normative population scores, are presented in Table 3. Neuroma pain patients had a significantly lower physical quality of life compared to the normative population (p<0.01). Upper extremity disability (DASH) and cold intolerance (CISS) scores were high (p<0.01). The mental quality of life (SF-36, MCS) was no different from a normal population and there was no increase in symptoms of psychopathology (SCL-90) compared to the normative population. After surgery, upper extremity function improved significantly (p=0.003). For the McGill pain score, only the evaluative dimension was significantly improved (PRI-e 6.8 vs. 5.4, p<0.05).
Table 3: Secondary outcomes.
Different pain modalities and their improvement following surgical treatment are shown in Table 4. Overall, all pain modalities improved. Pain at pressure was most frequently rated as severe prior to surgery and significantly improved after follow up (p<0.01). Pain with movement and hypersensitivity also improved (p=0.03). However, the number of patients with no complaints of hypersensitivity did not decrease following surgical treatment.
Table 4: Pain modalities.
For patients satisfied with the result of surgical treatment, the use of all types of pain medication had decreased (Table 5). In the unsatisfied group, the use of most types of pain medication increased after follow-up. The frequency of pain medication usage showed the same pattern (Table 6): in unsatisfied patients, the frequency of usage increased after follow up; while in satisfied patients, the frequency of pain medication usage clearly decreased following surgery (p=0.055). After follow-up, none of the patients with a good treatment result used pain medication on a daily basis, while 30% of unsatisfied patients did.
Table 5: Pain medication usage in satisfied and unsatisfied patients.
Table 6: Frequency of pain medication usage in satisfied and unsatisfied patients.
Data on pre-operative diagnostic nerve blocks were recorded for 18 patients at the outpatient clinic. There was no significant relationship between duration of pain and nerve block effect. The amount of remaining pain following diagnostic nerve block was significantly correlated with the post-operative pain score on the VAS (Fig. 3; Spearman's rho=0.538, p<0.05). Patients with an effective diagnostic nerve block (pain score less than 3.5) had significantly less pain following surgery compared to patients with an ineffective nerve block (VAS score 3.8 vs. 8.2, p=0.001). The positive predictive value of a successful diagnostic block on patient satisfaction was 66.7% and the negative predictive value was 83.3%.
Fig. 3.:
Graph: pain after diagnostic nerve block vs. post-operative pain. Spearman's rank correlation coefficient: 0.538, p < 0.05.
We have compared surgical techniques, injured nerves and types of injury between patients with a VAS score of below and at least 5 points, for the 18 patients presented in Fig. 3. We found no differences in surgical techniques (Pearson chi-square test: p=0.63), injured nerves (p=0.71) or types of injury (p=0.76).
Success rates of the various surgical procedures performed during the study can be found in Table 7. Neuromas of the SBRN led to the worst outcome, with only 33% of procedures providing satisfactory results. Post-operative satisfaction rates were not significantly different between the different affected nerves or performed surgical procedures.
Table 7: Patient satisfaction following different surgical procedures.
There were several prognostic factors for dissatisfying treatment results; the relative risks are presented in Table 8. Longer duration of pain was significantly correlated to a higher post-operative VAS score for pain (r=0.387, p=0.02) and the mean VAS score was higher after a duration of at least 48months (VAS 6.1 vs. 4.1). The proportion of patients with a duration of pain of 2years or more was 29%. The number of previous procedures did not influence primary outcome, neither did sex or socio-economic status. We found no relationship between time after surgery and post-operative VAS score (Pearson correlation coefficient: 0.202, p=0.25).
Table 8: Prognostic factors.
Before treatment, 19 patients (56%) were unemployed, including two patients who were retired, and after follow up six of these unemployed patients had returned to work. Patients that were employed during surgery demonstrated a greater decrease in VAS score than patients that were unemployed (p<0.05). Eighteen patients (53%) received workers compensation before surgery, this decreased to 10 (29%) after surgical treatment. A total of 13 patients (38%) were involved in litigation. Workers compensation and litigation were not predictive of the outcome.
Patients who smoked at the time of surgery had a significantly worse outcome than patients who did not smoke (Fig. 4, p=0.002). The RR of smoking for patient dissatisfaction was 2.10 (95% CI: 1.00–3.76). There was no confounding of the RR of smoking by duration of pain, employment status, CRPS II, age BMI or gender. However, there was effect modification present for all of these factors except CRPS II, with relative risks ranging from 0.88 to 3.86 between patient categories. Past smoking was not related to a worse outcome. Outcome was not related to the number of pack years smoked or the duration of smoking cessation prior to surgery, which ranged from 1 to 39years, with an average of 14years.
Fig. 4.:
Smoking status and pain decrease. Independent t-test: p = 0.002.
Post-operative satisfaction rates were 4/11 (36%) in CRPS (II) patients and 15/23 (65%) in non-CRPS patients. The mean decrease in VAS score was significantly different between these two groups: 0.45 for CRPS (II) patients and 2.67 for non-CRPS patients (p=0.01).
4. Discussion
Painful neuromas are often therapy resistant. It is relatively unknown that in some patients, peripheral nerve surgery can provide a permanent effect on pain relief, as opposed to the life-long use of analgesic medication or medical devices (e.g. nerve stimulators).
This prospective follow-up study was performed to evaluate the result of treatment on multiple outcome domains and to establish prognostic factors for insufficient pain relief following surgical treatment. We found that 56% of patients were satisfied with treatment results. There was a significant decrease in pain and disability and little or no improvement in cold intolerance, quality of life, or symptoms of psychopathology. Evaluating patient and surgery specific determinants, we found several prognostic factors predictive of insufficient pain relief including unemployment, nicotine use and poor pain relief following diagnostic nerve block.
To accurately study the effect of treatment for neuropathic pain, the use of appropriate outcome measures is essential [19]. Most studies performed in the area of neuroma pain focus on only one aspect of treatment outcome [2,3,21,22,26]. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommended 6 core outcome domains that should be considered in chronic pain research: pain; physical functioning; emotional functioning; improvement and satisfaction with treatment; other symptoms and adverse events during treatment; and patients’ disposition and characteristics [52]. We assessed all of these areas using previously validated, reliable measures.
Reliable pain measurement is difficult, since pain is a highly subjective symptom. Other studies often use ill defined or non validated outcome measures for pain [6,17,21,32,41,51]. We used the 10cm VAS, with a known good test–retest reliability, to assess pain pre- and post-operatively. Cut-off scores for a reliable and clinically relevant decrease in pain on the VAS were calculated using the method proposed by Jacobson et al. [23]. We observed that these cut-off points may in some cases be too stringent.
Remaining or recurrent pain after surgical neuroma treatment can be explained by secondary displacement of the translocated neuroma, failure to identify the presence of more than one neuroma in the same patient [32], or injury of neighboring nerve branches. Following complete neurectomy of the injured nerve, adjacent nerves may start to transmit sensory signals from the denervated skin area [1]. This process is desirable for normal sensory recovery, but can lead to recurrent or sustained pain in surgically treated neuroma pain patients. There is increasing evidence that hyperalgesia is independent of input from injured afferents, suggesting that ectopic activity originating from a neuroma is not necessary for the development of hyperalgesia [9,11,31]. As previously described by Stokvis et al. [49], patients surgically treated for a painful neuroma in the upper extremity showed a significant decrease in spontaneous pain, but not in cold-intolerance, or thermal hyperalgesia. In our study, symptoms of hypersensitivity improved to some extent. However, the number of patients without any hypersensitivity did not decrease following surgical treatment.
Careful patient selection for surgical treatment is critical for a successful outcome of neuroma pain treatment [54]. In the diagnostic workup of neuroma pain patients, a diagnostic nerve block with 1% lidocaine is often performed [33]. It is proposed that insufficient pain relief following a diagnostic block is a contraindication to surgery [32]. Unfortunately, statistically significant evidence for the diagnostic or prognostic value of peripheral nerve blocks for neuroma pain diagnosis has, to our knowledge, not been described in literature before. We found the effect of a diagnostic peripheral nerve block to be significantly predictive of the amount of pain following surgery for painful neuromas. For patients with a good response to the block, success chances were significantly higher. We should take into account the fact that the majority of patients with an unsuccessful nerve block was not surgically treated and therefore not included in our study. This may bias the predictive value of an unsuccessful diagnostic nerve block. It emphasizes the need for placebo controlled studies in determining the true predictive value of this often used diagnostic tool [29].
Longer duration of pain was significantly correlated to a higher post-operative VAS score for pain. This is a common finding in literature and may be explained by changes in pain processing in the central nervous system (CNS) that can occur during the chronic phase of neuropathic pain [48]. However, patients with a highly therapy resistant pain problem will subsequently have a longer duration of pain and more surgical procedures, regardless of the cause.
Employment status was related to a better outcome and the literature on neuroma pain outcome supports this result [48]. The finding by Suter [50] that employed patients had less severe symptoms prior to treatment was also present in our patient population; and we also found a significantly greater improvement in pain score for employed patients. Suter stated that employed patients experience a feeling of satisfaction that alleviates the perception of pain and disability and that working facilitates recovery from injury. Therefore, it would be valuable to focus on activity and employment in the treatment and rehabilitation of chronic pain patients [10].
Nicotine is known to have central analgesic properties in humans, but paradoxically, also has peripheral nociceptive effects. In animal-experimental research, chronic nicotine use produces a stable, long-lasting, mechanical hypersensitivity resulting from peripheral nerve injury [24]. However, clinical research is to our knowledge restricted to a single case series with two patients. In the study by Richards et al. [43], patients experienced a marked reduction in neuropathic pain following smoking cessation and their pain returned once they resumed smoking. In our study, smokers had a significantly worse outcome, with less reduction in pain and a lower satisfaction compared to non smokers.
The observation of effect modification by multiple patient-specific factors makes the adverse effect of smoking in our patient population fairly difficult to interpret. Although the exact mechanism of nicotine on neuropathic pain needs to be elucidated, smoking should be discouraged in patients sustaining plastic surgery [37,56]: chronic exposure to cigarette smoke produces profound changes in physiology that may contribute to peri-operative morbidity [56]. It is known to impair digital blood flow and wound healing in the hand [39,53] and increases the risk of post-operative wound-related complications, such as dehiscence and wound infection [40,56]. Since previous smokers did not share the adverse effect of current smoking on the outcome, smoking cessation is a potentially valuable intervention to achieve satisfactory pain relief. Further experimental and clinical studies are needed to investigate the effect of smoking (cessation) on peripheral neuropathic pain treatment.
We observed the presence of CRPS symptoms to be another important prognostic factor for dissatisfaction with surgical treatment. However, we would not necessarily advice against operating on these patients. In a study by Dellon et al. [8] 32 out of 40 patients with CRPS II were successfully treated with peripheral nerve surgery. In our patient population, 36% of patients with CRPS II was satisfied with the result of surgery on their symptoms. Therefore, peripheral nerve surgery still provides an option for permanent pain relief in patients with chronic debilitating complaints. However, these patients should be aware of their reduced chances for successful pain relief.
There are some limitations to this study that should be discussed. Our study population existed of patients referred to a tertiary referral center for expertise in the field of neuropathic pain treatment, sometimes following multiple ineffective treatments. This is likely reflected in the severe and therapy resistant nature of our patients’ complaints and, therefore, negatively influences outcome compared to other medical centers and neuropathic pain disorders.
We included neuropathic pain patients with neuromas of any of the peripheral sensory nerve branches in the upper extremity. This has provided a somewhat heterogeneous patient group, with some subgroups of more rarely affected sensory nerve branches, but increased the overall applicability of our outcomes.
Given the reasonably low incidence of painful neuromas, our study was based on a relatively large number of patients. Most studies that have been performed evaluating painful neuroma treatments comprised case series with small patient numbers [12,16,22,25–27,30,35,46,47] or had a retrospective design [28,42,51].
Our study was conducted as a prognostic follow-up study. This type of study is readily used to accurately study prognostic factors for treatment outcome. Since data collection was prospective, information bias was largely avoided and response rates were high. We were able to compare pre-and post-operative findings for all included patients, with complete follow up for 34 out of 35 patients returning the primary questionnaire.
Neuroma pain following upper extremity nerve injury remains a difficult problem; patients experience high disability and low quality of life. Surgical treatment can effectively decrease pain, disability and workers’ compensation rates. Unfortunately, insufficient pain relief following surgical neuroma treatment is a common finding. Our results could lead to improved patient selection and treatment strategies. If a diagnostic nerve block is ineffective in relieving pain, patients will most likely not benefit from surgical treatment. Patients should be encouraged to focus on activity and employment instead of their symptoms. Smoking should be discouraged in patients who will undergo surgical neuroma treatment.
Conflict of interest statement
There are no conflicts of interest.
References
[1] Aszmann OC, Muse V, Dellon AL. Evidence in support of collateral sprouting after sensory nerve resection.
Ann Plast Surg. 1996;37:520-525.
[2] Atherton DD, Elliot D. Relocation of neuromas of the lateral antebrachial cutaneous nerve of the forearm into the brachialis muscle.
J Hand Surg Eur Vol. 2007;32:311-315.
[3] Atherton DD, Fabre J, Anand P, Elliot D. Relocation of painful neuromas in Zone III of the hand and forearm.
J Hand Surg Eur Vol. 2008;33:155-162.
[4] Atherton DD, Taherzadeh O, Facer P, Elliot D, Anand P. The potential role of nerve growth factor (NGF) in painful neuromas and the mechanism of pain relief by their relocation to muscle.
J Hand Surg Br. 2006;31:652-656.
[5] Balcin H, Erba P, Wettstein R, Schaefer DJ, Pierer G, Kalbermatten DF. A comparative study of two methods of surgical treatment for painful neuroma.
J Bone Joint Surg Br. 2009;91:803-808.
[6] Barbera J, Albert-Pamplo R. Centrocentral anastomosis of the proximal nerve stump in the treatment of painful amputation neuromas of major nerves.
J Neurosurg. 1993;79:331-334.
[7] Curtin C, Carroll I. Cutaneous neuroma physiology and its relationship to chronic pain.
J Hand Surg Am. 2009;34:1334-1336.
[8] Dellon AL, Andonian E, Rosson GD, CRPS I. Of the upper or lower extremity: surgical treatment outcomes.
J Brach Plexus Peripheral Nerve. 2009;4:1-15.
[9] Dorsi MJ, Chen L, Murinson BB, Pogatzki-Zahn EM, Meyer RA, Belzberg AJ. The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia.
Pain. 2008;134:320-334.
[10] Dworkin RH, Handlin DS, Richlin DM, Brand L, Vannucci C. Unraveling the effects of compensation, litigation, and employment on treatment response in chronic pain.
Pain. 1985;23:49-59.
[11] Eschenfelder S, Habler HJ, Janig W. Dorsal root section elicits signs of neuropathic pain rather than reversing them in rats with L5 spinal nerve injury.
Pain. 2000;87:213-219.
[12] Evans GR, Dellon AL. Implantation of the palmar cutaneous branch of the median nerve into the pronator quadratus for treatment of painful neuroma.
J Hand Surg [Am]. 1994;19:203-206.
[13] Foltan R, Klima K, Spackova J, Sedy J. Mechanism of traumatic neuroma development.
Med Hypotheses. 2008;71:572-576.
[14] Forouzanfar T, Weber WE, Kemler M, van Kleef M. What is a meaningful pain reduction in patients with complex regional pain syndrome type 1?
Clin J Pain. 2003;19:281-285.
[15] Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician.
CMAJ. 2006;175:265-275.
[16] Goldstein SA, Sturim HS. Intraosseous nerve transposition for treatment of painful neuromas.
J Hand Surg [Am]. 1985;10:270-274.
[17] Gorkisch K, Boese-Landgraf J, Vaubel E. Treatment and prevention of amputation neuromas in hand surgery.
Plast Reconstr Surg. 1984;73:293-299.
[18] Goubert L, Crombez G, Van Damme S, Vlaeyen JW, Bijttebier P, Roelofs J. Confirmatory factor analysis of the Tampa Scale for Kinesiophobia: invariant two-factor model across low back pain patients and fibromyalgia patients.
Clin J Pain. 2004;20:103-110.
[19] Harden N, Cohen M. Unmet needs in the management of neuropathic pain.
J Pain Symptom Manage. 2003;25:S12-S17.
[20] Harden RN. Chronic neuropathic pain. Mechanisms, diagnosis, and treatment.
Neurologist. 2005;11:111-122.
[21] Hazari A, Elliot D. Treatment of end-neuromas, neuromas-in-continuity and scarred nerves of the digits by proximal relocation.
J Hand Surg [Br]. 2004;29:338-350.
[22] Herbert TJ, Filan SL. Vein implantation for treatment of painful cutaneous neuromas. A preliminary report.
J Hand Surg [Br]. 1998;23:220-224.
[23] Jacobson NS, Roberts LJ, Berns SB, McGlinchey JB. Methods for defining and determining the clinical significance of treatment effects: description, application, and alternatives.
J Consult Clin Psychol. 1999;67:300-307.
[24] Josiah DT, Vincler MA. Impact of chronic nicotine on the development and maintenance of neuropathic hypersensitivity in the rat.
Psychopharmacology (Berl). 2006;188:152-161.
[25] Kakinoki R, Ikeguchi R, Atiyya AN, Nakamura T. Treatment of posttraumatic painful neuromas at the digit tip using neurovascular island flaps.
J Hand Surg Am. 2008;33:348-352.
[26] Kakinoki R, Ikeguchi R, Matsumoto T, Shimizu M, Nakamura T. Treatment of painful peripheral neuromas by vein implantation.
Int Orthop. 2003;27:60-64.
[27] Kon M, Bloem JJ. The treatment of amputation neuromas in fingers with a centrocentral nerve union.
Ann Plast Surg. 1987;18:506-510.
[28] Laborde KJ, Kalisman M, Tsai TM. Results of surgical treatment of painful neuromas of the hand.
J Hand Surg [Am]. 1982;7:190-193.
[29] Lamacraft G, Cousins MJ. Neural blockade in chronic and cancer pain.
Int Anesthesiol Clin. 1997;35:131-153.
[30] Lanzetta M, Nolli R. Nerve stripping: new treatment for neuromas of the palmar cutaneous branch of the median nerve.
J Hand Surg [Br]. 2000;25:151-153.
[31] Li Y, Dorsi MJ, Meyer RA, Belzberg AJ. Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers.
Pain. 2000;85:493-502.
[32] Lluch A. Treatment of radial neuromata and dysesthesia.
Tech Hand Up Extrem Surg. 2001;5:188-195.
[33] Mackinnon SE, Dellon AL. Results of treatment of recurrent dorsoradial wrist neuromas.
Ann Plast Surg. 1987;19:54-61.
[34] Mackinnon SE, Dellon AL, Hudson AR, Hunter DA. Alteration of neuroma formation by manipulation of its microenvironment.
Plast Reconstr Surg. 1985;76:345-353.
[35] Mass DP, Ciano MC, Tortosa R, Newmeyer WL, Kilgore ES Jr. Treatment of painful hand neuromas by their transfer into bone.
Plast Reconstr Surg. 1984;74:182-185.
[36] Melzack R. The McGill Pain Questionnaire: major properties and scoring methods.
Pain. 1975;1:277-299.
[37] Moller AM, Villebro N, Pedersen T, Tonnesen H. Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
Lancet. 2002;359:114-117.
[38] Morley S, Williams A, Hussain S. Estimating the clinical effectiveness of cognitive behavioural therapy in the clinic: evaluation of a CBT informed pain management programme.
Pain. 2008;137:670-680.
[39] Mosely LH, Finseth F. Cigarette smoking: impairment of digital blood flow and wound healing in the hand.
Hand. 1977;9:97-101.
[40] Myles PS, Iacono GA, Hunt JO, Fletcher H, Morris J, McIlroy D, Fritschi L. Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
Anesthesiology. 2002;97:842-847.
[41] Novak CB, Anastakis DJ, Beaton DE, Katz J. Evaluation of pain measurement practices and opinions of peripheral nerve surgeons.
Hand (NY). 2009;4:344-349.
[42] Novak CB, van Vliet D, Mackinnon SE. Subjective outcome following surgical management of upper extremity neuromas.
J Hand Surg [Am]. 1995;20:221-226.
[43] Richards JS, Kogos SC Jr, Ness TJ, Oleson CV. Effects of smoking on neuropathic pain in two people with spinal cord injury.
J Spinal Cord Med. 2005;28:330-332.
[44] Ring D, Kadzielski J, Fabian L, Zurakowski D, Malhotra LR, Jupiter JB. Self-reported upper extremity health status correlates with depression.
J Bone Joint Surg Am. 2006;88:1983-1988.
[45] Schauenburg H, Strack M. Measuring psychotherapeutic change with the symptom checklist SCL 90 R.
Psychother Psychosom. 1999;68:199-206.
[46] Sood MK, Elliot D. Treatment of painful neuromas of the hand and wrist by relocation into the pronator quadratus muscle.
J Hand Surg [Br]. 1998;23:214-219.
[47] Stahl S, Rosenberg N. Surgical treatment of painful neuroma in medial antebrachial cutaneous nerve.
Ann Plast Surg. 2002;48:154-158. [discussion 158–60].
[48] Stokvis A, Coert JH, van Neck JW. Insufficient pain relief after surgical neuroma treatment: prognostic factors and central sensitisation.
J Plast Reconstr Aesthet Surg. 2010;63:1538-1543.
[49] Stokvis A, Ruijs AC, van Neck JW, Coert JH. Cold intolerance in surgically treated neuroma patients: a prospective follow-up study.
J Hand Surg Am. 2009;34:1689-1695.
[50] Suter PB. Employment and litigation: improved by work, assisted by verdict.
Pain. 2002;100:249-257.
[51] Tupper JW, Booth DM. Treatment of painful neuromas of sensory nerves in the hand: a comparison of traditional and newer methods.
J Hand Surg [Am]. 1976;1:144-151.
[52] Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad AR, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.
Pain. 2003;106:337-345.
[53] van Adrichem LN, Hovius SE, van Strik R, van der Meulen JC. The acute effect of cigarette smoking on the microcirculation of a replanted digit.
J Hand Surg [Am]. 1992;17:230-234.
[54] Vernadakis AJ, Koch H, Mackinnon SE. Management of neuromas.
Clin Plast Surg. 2003;30:247-268. [vii].
[55] Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.
Med Care. 1992;30:473-483.
[56] Warner DO. Perioperative abstinence from cigarettes: physiologic and clinical consequences.
Anesthesiology. 2006;104:356-367.
