Gender differences after lumbar sequestrectomy: a prospective clinical trial using quantitative sensory testing

The study was purely observational. Pain management was not delayed or altered by participation in this study. All subjects gave their informed consent. The study was approved by the Local Ethics Committee of the Medical University of Innsbruck. Consecutive patients were considered for inclusion if they had a single-level disc herniation confirmed on magnetic resonance imaging (MRI) and a medically refractory radiating pain and/or motor deficits in the corresponding nerve root distribution area of L3 to S1. All patients had an indication for sequestrectomy according to the guidelines of the German Society of Neurosurgery and the German Society of Orthopaedics and Orthopaedic Surgery. No previous back surgery had been performed in any of the patients. None of the included patients had a history of peripheral nervous system disorders. Neither metabolic nor toxic damage of the peripheral nerves was revealed. In female patients, no adjustment for menstrual phase was made at the time of testing. The study group consisted of 21 women and 32 men.

Preoperative magnetic resonance imaging (MRI) of the lumbar spine was performed in a standardised fashion on a 3.0-T MRI scanner (Siemens, Verio). The protocols included sagittal T1-TSE and T2-TSE, and axial T1-TSE and PD/T2-TSE. Each MRI was examined for the evidence of disc degeneration (Pfirrmann degeneration grade) and degenerative changes of the intervertebral endplates (Modic changes) by an independent neuroradiologist, blinded to the clinical signs and symptoms [14, 15].

The prospectively planned evaluation included a detailed medical history, a physical examination, and various questionnaires. All data were recorded the day before surgery, within 1 week, 6 and 12 months after surgery. The visual analog scale (VAS) was additionally evaluated on the first, second and third postoperative day. The Beck Depression Inventory (BDI) was used for measuring the severity of depression and responsiveness to treatment [16]. To identify neuropathic pain components, the painDETECT-questionnaire (PD-Q) was performed [17]. The degree of disability and the patient’s satisfaction was assessed with the Oswestry Disability Index (ODI) [18] and the Core Outcome Measure Index (COMI) [19]. Furthermore, EQ-5D thermometer was used to assess the quality-adjusted health status from 1 to 100 (best) [20]. Neurological status and the quality and quantity of current pain medication in accordance to the WHO guidelines for pain treatment, including nerve root and facet joint injections, were documented.

The QST was performed pre- and postoperatively by a single investigator. The thermal tests were performed using a Sensory Analyzer TSA-II (Medoc, Israel). Cold and warm detection thresholds were measured first (CDT, WDT), then cold pain and heat pain thresholds (CPT, HPT). The mechanical detection threshold (MDT) was measured with a standardised set of modified von Frey hairs (Somedic, Sweden) that exert forces upon bending between 0.25 and 512 mN. The vibration detection threshold (VDT) was performed with a Rydel-Seifer tuning fork (64 Hz, 8/8 scale). The mechanical pain threshold (MPT) was measured by a custom made pinprick set with forces from 8 to 512 mN. Mechanical pain sensitivity (MPS) was assessed using the same pinprick stimuli to obtain a stimulus response function for pinprick evoked pain. Subjects were asked to give a pain rating for each stimulus on a 0–10 numerical rating scale (NRS “0” indicating “no pain” and “10” indicating the “most intense pain imaginable”). A pressure gauge device (FDK 20, Wagner Instruments, USA) was used to measure the pressure pain threshold (PPT) [21, 22].

Surgery was performed after induction of general endotracheal anaesthesia and with the assistance of an operating microscope (Pentero, Carl Zeiss Co.) while the patient was in a prone position, by two surgeons in a standardised manner. The spinal canal harbouring the sequestrated disc material was exposed by performing a minimal inter-laminar fenestration in cases of non-dislocated or caudally herniated disks. In cases of cranially herniated disks, a translaminar approach was undertaken. Based on results of previous trials only the herniated material was removed and the herniated space was not entered, if at all possible [2]. Surgery related complications and postoperative complications like re-operations, recurrent disc herniations, infection or hematoma were recorded.

All patients with a complete preliminary examination were considered for inclusion into the study population. All values were expressed as mean ± SD. The Kolmogorov–Smirnov test was used for testing normal distribution. The unpaired Student’s t test, Mann–Whitney U test and Fisher’s exact test were used to analyse differences in clinical and demographic characteristics and in clinical outcome variables. A p value <0.05 was considered statistically significant. All statistical evaluations were performed with SPSS Version 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0, NY: IBM Corp.). Figures were designed using GraphPad Prism (version 5.0 for Mac OS X, GraphPad Software, La Jolla California USA, http://​www.​graphpad.​com).

56 patients that met the initial in- and exclusion criteria were prospectively included in the trial. Three patients withdrew the informed consent. Participants with intra-operative nerve root damage or postoperative complications (e.g. recurrent disc herniations) were excluded from the study as these factors would have influenced the outcome data. Therefore, the overall rate of 6 and 12 months follow-up was 80.4% and of 12 months was 69.7%, respectively. The most common reason for exclusion was a recurrent disc herniation in 16%. The drop out rate was three times higher for men than for women. In all of these patients, a second sequestrectomy was performed. Two men developed a second reherniation and underwent spinal fusion one year thereafter. Loss of follow-up of 30% at one year creates a significant void in the results and could have potentially lead to a type 1 error.

The preoperative demographic details are presented in Table 1. There were no significant intergroup differences in the preoperative demographic data. In twelve patients, periradicular steroid application was applied within 30–90 days preoperatively for pain management. 66% of female and 62% of male patients took analgesics on a regular basis before surgery (Table 2). Except for one man who took 150 mg pregabalin daily, no permanent pain medication was used; none of the patients received a nerve root or facet joint injection, postoperatively. There was no difference in total operation time in minutes (73.7 min. ± 26.0 for women vs. 73.6 min. ± 32.2 for men) or intra-operative radiation time in seconds between genders (5.0 s. ± 8.4 vs. 5.0 s. ± 6.6), respectively. The area dose product in Gy cm2 was lower in female than in male patients (29.3 ± 22.1 vs. 54.4 ± 34.8, p < 0.05). As preoperative steroid injections in 12 patients could have potentially influenced the outcome after surgery, statistical analyses were performed between the two groups. Postoperatively, there were no significant differences, neither in the QST data nor in the clinical outcome scores.

The results of the QST thresholds are presented in Fig. 1. HPT and PPT were preoperatively found to be lower in female than in male patients: HPT 46.1 °C ± 8.0 and PPT 5.6 kg ± 2.7 in females vs. HPT 48.8 °C ± 2.1 and PPT 7.5 kg ± 2.6 in males (p < 0.05). ALL did only occur in females and disappeared after one year follow-up, a significant gender difference was not found. VDT reached a significant difference at 1 week follow-up, 6.7 Hz ± 1.3 for women and 5.6 Hz ± 2.2 for men, respectively (p < 0.05). MDT differed significantly 12 months postoperative between genders: 1.8 mN ± 1.8 in female, 15.5 mN ± 29.5 in male participants (p < 0.05). Pre- and postoperative thermal detection thresholds (CDT and WDT) and MDT tend to be lower in women than in men (p > 0.05). PPT differed significantly between genders at 1 week, 6 and 12 months follow-up period (p < 0.05).

Leg pain on VAS was rated insignificantly higher in female than in male patients, whereas low back pain revealed to be higher in male patients (p > 0.05). At admission the mean overall VAS was detected 5.8 ± 2.0 in women and 4.4 ± 2.6 in men (p < 0.05), respectively (see Fig. 2). Analysis of BDI data demonstrated no significant gender differences, but there was a trend towards higher depression scores in females. ODI indicated a trend to lower disability in women preoperatively, but adjusted the first week after surgery (p > 0.05). There was also a trend in PD-Q that indicated higher neuropathic pain components, preoperatively (19.3 ± 5.7 vs. 16.3 ± 6.5; p > 0.05). Additionally, women showed an insignificantly lower quality of health in EQ-5D thermometer preoperatively, 1 week and 6 months postoperatively (p > 0.05). For more details see Table 3.