Total patient population
In total 2,480 pain patients were enrolled in the study by 177 general practitioners (GPs) and 97 specialists. The total number of patients that could have been expected was not reached since 63 physicians (28 GP's and 35 specialists) failed to fulfil the inclusion target, and a number of questionnaires (n = 493) had to be discarded due to incompleteness of the data. Reasons for these failures are probably the work load and the strict time schedule of this protocol. Around two thirds of the patients (n = 1,649) were treated by a GP, while 831 patients (34%) were being treated by a specialist. More than half of the participating pain patients (59.6%) were women. The mean age of the patients was 58.2 years (standard deviation, SD, = 15.7). The average duration of the pain amounted to 3.0 years (SD = 4.4), with a range from less than three months to 60 years (diabetic neuropathy). Almost one third of the patients (28%) reported their pain having lasted from six months to three years.
Data on the underlying pathology were obtained for 2,436 out of 2,480 pain patients (98%). A total of 65.2% of the patients had one underlying cause of pain, while in 25.4% of patients two underlying disorders could be identified. Three or more pathologies were reported by 9.4% of the patients. The most prevalent causes of pain consisted of lumbar pain (32.1% of patients), followed by osteoarthritis (OA) (24.2%), post-traumatic lesions (13.4%), diabetes mellitus (10.4%), post-surgical lesions (9.5%), osteoporosis (7.6%), complex regional pain syndrome (CRPS) (7.3%), and post-herpetic neuralgia (6.7%) (Fig. ). The most frequently described combination of diagnoses was lumbar pain in combination with OA (reported in 6.0% of patients), followed by lumbar pain combined with post-surgical lesions (1.9% of patients). It Is important to mention that there were no statistical differences between the pathologies diagnosed by the GP's or the specialists, with both physicians groups reporting similar percentages for the different pathologies.
Figure 1 Identified causes of pain. Possible underlying causes of pain in (1) all patients pooled (n = 2,436) and (2) the patients with a LANSS pain score ≥ 12 (n = 1,163). Patients may have multiple underlying pathologies. DN: diabetic neuropathy, TS: (more ...)
Type of pain symptoms
Spontaneous pain was present in 96.5% of the patients. A total of 61.5% of patients seeking medical help reported a combination of spontaneous and provoked pain symptoms (61.5%), while 37.8% reported spontaneous pain as their only symptom. Finally, 0.7% of patients reported only provoked pain symptoms. Spontaneous pain was mainly described in terms of throbbing pain (61.3%), a burning sensation (47.9%), or abnormal and disagreeable (painful) sensations (dysaesthesia) (47.8%). Less frequent manifestations of spontaneous pain comprised cutting-lacerating pain (31.8% of patients), electric shock sensation (22.8%), stab sensation (18.8%), and abnormal but not disagreeable sensation (paraesthesia) (17.3%). The majority of the patients with spontaneous pain symptoms (57.7%) identified two or three terms to describe their symptoms. The combination of a burning sensation, throbbing pain and dysaesthesia was the most frequently reported combination (6.4% of the patients with spontaneous pain), followed by a burning sensation together with dysaesthesia (4.5%), throbbing pain with dysaesthesia (4.3%), and throbbing pain in combination with cutting-lacerating pain symptoms (4.0%).
Evoked pain was mostly present as allodynia (40.3%), hyperalgesic symptomatology only (10.3%), or mixed allodynic/hyperalgesic symptoms (47.0%). Touch-evoked allodynia was most common (71.7% of all patients suffering from provoked pain). These allodynic symptoms were induced by several triggers, such as contact with clothes (38.8%), or allodynia in the shower or in bath (15.2%), followed by painful symptoms resulting from wind blowing against the face (12.5%) and during shaving (5.4%). Pin-prick hyperalgesia was found to be the most common form of hyperalgesia, being present in more than half (52.5%) of all patients suffering from hyperalgesic symptoms. Other forms of hyperalgesia were reported in 2.5% of the patients. Once more, as observed previously with spontaneous pain, a majority of patients (61.6%) reported more than one subtype of provoked pain. The most frequently reported combinations of provoked pain symptoms were touch-evoked allodynia combined with pin-prick hyperalgesia (12.5% of the patients with provoked pain symptoms), followed in second place by touch-evoked allodynia combined with allodynia induced by clothing and pin-prick induced hyperalgesia (11.7%).
Subgroups of patients: LANSS scale pain score <12 versus LANSS scale pain score ≥ 12
Of the total number of patients enrolled in this survey for whom a LANSS pain score was recorded (n = 2,464), 1,163 patients (47.2%) presented with a LANSS score of 12 or more (LANSS ≥ 12 group), which strongly suggests the presence of a pain component of neuropathic origin [11
]. Demographic data were similar across the subgroups, showing no significant differences in age (mean 57.7 yrs, SD = 15.5 vs. 58.6 yrs, SD = 15.8; NS), gender (58.5% vs. 60.5% women; NS), or duration of pain (mean 3.1 yrs, SD = 4.1 vs. 2.9 yrs, SD = 4.7; NS) between the LANSS ≥ 12 group and the patients with a LANSS score < 12 (LANSS < 12 group) respectively. We did not find any significant association between LANSS score and duration of the pain in either subgroup (data not shown).
LANSS scale pain scores in relation to the underlying pathologies
Diseases that are known to be associated with NeP such as diabetes mellitus (mean LANSS score = 14.4), syringomyelia (17.5), thalamic syndrome (18.1), post-herpetic neuralgia (17.2), and CRPS type 2 (16.6) yielded higher mean LANSS scores than pathologies that are generally considered to be associated with NocP, e.g. OA (mean LANSS score = 8.7) or osteoporosis (9.2). Further support for the efficacy of the LANSS scale in detecting NeP can be found in the results of the odds ratio (OR) analysis, in which 1,580 patients reporting only one underlying cause of pain were included. Indeed, the OR of having a LANSS score ≥ 12 for patients suffering from a typical nociceptive pathology, such as OA or osteoporosis, amounted to only 0.1 and 0.2 respectively, while the OR for NeP conditions such as diabetic neuropathy, multiple sclerosis, post-herpetic neuralgia and CRPS were 3.0, 6.9, 5.4, and 3.1 respectively (Fig. ).
Figure 2 Calculated Odds ratios. Odds ratios for the various pathologies having a LANSS score ≥ 12 with 95% CI. Only patients with one cause of pain included (n = 1,510). Scale on x-axis has been cut off at 10 for better visualisation (note the logarithmic (more ...)
However, assessment of validity can not only be determined on the basis of averages of the LANSS scores obtained for each clinical entity. In evident NeP syndromes the LANSS Pain Scale failed to correctly identify (score < 12) 25/133 of diabetic patients, 20/137 PHN patients, 6/42 patients suffering from thalamic syndrome, 9/59 patients with carpal canal syndromes, 9/75 CRPS patients, and 3/26 MS patients (all with only one pain complaint). This amounts to a total number of failures of 72/472 (15,2%). In nociceptive syndromes, the LANSS Pain Scale produced high scores (≥ 12) in 26/169 OA patients, 68/316 patients suffering from lumbar pain, and 7/26 osteoporotic patients. In these three non-neuropathic conditions, 101/511 received false high LANSS scores (19,8%). When considering the above mentioned NeP and NocP syndromes, the LANSS Pain Scale was able to correctly identify 82,4% (810/983) of patients with one pain complaint, representing 84,7% sensitivity and 80,2% specificity.
Type of pain symptoms
The pattern in prevalence of specific subtypes of pain is clearly different between the two subgroups of patients. Data on type of pain were available for 1,245 patients belonging to the LANSS < 12 group and for 1,140 patients of the LANSS ≥ 12 group. Eighty-nine percent of the patients belonging to the LANSS ≥ 12 group reported a combination of stimulus-evoked and spontaneous pain, against only 36.2% of those from the LANSS < 12 group. In contrast, 63.2% of the patients of the LANSS < 12 group reported only spontaneous pain, against 10.2% of those in the LANSS ≥ 12 group. Isolated evoked pain complaints were rather uncommon and their prevalence was similar for both subgroups (0.6% and 0.8% of patients from the LANSS < 12 and ≥ 12 groups respectively). In addition, the various manifestations of spontaneous and provoked pain syndromes were described in different terms by the patients belonging to the different subgroups. Pain types indicative of NeP occurred much more frequently in patients with LANSS ≥ 12 than in those with a score of < 12 (Table ). Indeed, more than twice the number of patients from the LANSS ≥ 12 group than patients from the LANSS < 12 group described their pain as a burning sensation, dysaesthesia, and electric shock sensation (Table ). A stabbing sensation was also significantly more prevalent among the patients belonging to the LANSS ≥ 12 group compared to those belonging to the LANSS < 12 group (22.9% vs. 15.1% of patients respectively, p < 0.001). Most conditions of allodynia were also significantly more prevalent among patients from the LANSS ≥ 12 group than among those from the LANSS < 12 group (Table ). Pin-prick evoked hyperalgesia was prevalent in about twice as many patients in the LANSS ≥ 12 group as in those in the LANSS < 12 group. In contrast, the occurrence of other forms of hyperalgesia was not significantly different between the two subgroups of patients (Table ).
Comparison of type of pain complaints between patients with LANSS score ≥ 12 and patients with a LANSS score < 12
Impact of pain on sleep and daily life
Only patients belonging to the LANSS ≥ 12 group completed this part of the survey. Data on the effect of pain on sleep was recorded for 1,148 of patients belonging to this subgroup. The mean score for sleep disturbance on the VAS amounted to 5.2 (SD = 2.6) on a scale from 0 to 10, with 10 indicating a maximal sleep disturbance during the past 24 h. It is important to mention that only 8.2% of all patients completing the queries about their sleep quality failed to report any negative impact of the pain symptoms on their quality of sleep. Lumbar pain in combination with post-surgical lesions was identified as the medical condition that caused the most sleep disturbance with an average VAS score of 6.0 (SD = 2.1, n = 27). The lowest mean VAS score was found in the group of multiple sclerosis patients (mean VAS score = 4.1 SD = 2.6, n = 22). Patients with combined complaints of spontaneous and provoked pain had a mean VAS score of 5.3 (SD = 2.6; n = 1,000), whereas patients with only spontaneous complaints had a mean VAS score of 4.8 (SD = 2.4; n = 111). Hyperalgesia and allodynia caused similar degrees of sleep disturbance (mean VAS = 4.4, SD = 2.3, n = 74 and mean VAS = 4.8, SD = 2.8, n = 320 respectively). When considering the type of sleep interference, the large majority of patients reported difficulties falling asleep (60.4%), interruption of sleep (72.1%), premature awakening (60.4%) and non-restorative sleep (66.7%). In addition, 93.6% of patients reported an impact on their activities of daily living. Most of the patients reported an influence on family life (77.5%), social activities (79.8%), spare time (81.8%) and professional activities (66.1%). It should be noted that 41.4% even reported influence of their pain on all of these aspects.
On top of the clinical examination, the large majority of patients in the LANSS ≥ 12 group received complementary technical investigations to obtain final confirmation of the diagnosis of NeP. Data were available for 1,125 of the patients in the LANSS ≥ 12 group, and revealed that 1,002 of these (89.1%) were subject to one of more supplementary examinations (besides clinical examination). The most commonly performed technical investigations were electromyography (68.9% of patients), followed by radiography (59.2%), CT/MRI scan (56.2%), lab tests (51.4%), bone scan (31.4%), and a sensory evoked potential test (8.5%). Of all patients subject to additional testing, 77.8% received more than one test. Based on the results of this study, post-herpetic neuralgia is apparently perceived as the most straight-forward clinical diagnosis since only less than half of these patients (44.9%) received additional tests. In all other disorders a large majority of patients was subject to additional exams. Interestingly, our study results clearly indicate that the actual number of additional tests that were carried out is highly dependent on the underlying pathology. Most patients with carpal canal syndrome (74.2%; 23 out of 31 patients) and almost half of those suffering from diabetes (46.1%; 41 out of 89) received only one additional test, while the majority of those with another underlying pathology received two or more exams (Table ).
Percentage of patients undergoing one or more additional tests in relation to the underlying pathology in patients with LANSS ≥ 12 (n = 1,163)
Pharmacological treatment of the pain
In total, 95.1% of patients (n = 1,084) in the LANSS ≥ 12 group had received pharmacological treatment prior to enrolment in this survey. In almost all patients this (previous) treatment consisted of prescription drugs (88.5% of the patients) or a combination of prescription and over-the-counter (OTC) drugs (9.8%). Paracetamol was the most commonly prescribed drug (67.1% of the patients) followed by drugs belonging to the non-selective non-steroidal anti-inflammatory drugs (NSAID)/cyclo-oxygenase-2 specific (COX-2) inhibitors (61.4%). On the third place came the antidepressant agents (41.4%). Less common were opioids (although still taken by about 30.5% of the patients), anti-epileptic drugs (AED) in 18.0% of the patients, and finally acetylic salicylic acid (4.2%). Similar treatment patterns were found in patients consulting a GP or a specialist. However, patients treated by specialists received more treatments using AED than when treated by primary care physicians (25.5% of patients in specialist care versus 14.4% in primary care). In contrast, the use of antidepressant drugs was more common in patients seeking help of primary care physicians than specialists (44.7% vs. 34.4%).
Only 24.1% of the patients had previously received one drug, while 38.2% had been prescribed a combination of two drugs, and 23.1% had even received three different drugs (Fig. ). Finally, 14.6% received a combination of four or more medications. When treated with a combination of analgesics, the most frequently used combination was paracetamol and NSAID/COX-2 inhibitors (14.6% of patients), followed by a combination consisting of NSAID/COX-2 inhibitors, paracetamol and antidepressive agents (8.9%). The use of paracetamol and NSAID was fairly similar across underlying conditions (data not shown) with about 60–75% of patients taking these drugs. In contrast, considerable variations in the prescription of opioids, AED and antidepressants were recorded across the various pathologies. Opioids were the predominant drugs in cancer pain conditions (62.8% of 47 cancer patients) as well as in patients with post-surgical lesions (44.0% of 134 patients). Antidepressant drugs were prescribed to many patients suffering from MS (56.7% of 32 patients), post-herpetic neuralgia (49.6% of 127 patients), and pain due to a cerebrovascular accident (post-CVA pain) (55.8% of 44 patients). AED were commonly taken by patients with post-CVA pain (48.8% of 44 patients), post-herpetic neuralgia (23.1% of 127 patients), post-surgical lesions (21.6% of 134 patients), and in patients suffering from diabetic neuropathy (18.6% of 160 patients).
Use of analgesic agents. Number of pharmacological agents prescribed before and after applying the LANSS pain scale evaluation in LANSS ≥ 12 group.
Future treatment options
When questioned about which specific future treatment options they considered appropriate for their patients, physicians indicated that they considered pharmacological treatment (either starting up or continuation) in 87.6% of the patients from the LANSS ≥ 12 group (n = 1,163). Interestingly enough, physicians stated that respectively 36.6% and 17.6% of the patients would be referred for physiotherapy and for psychosocial support.
Compared to previous treatment regimens, physicians indicated that future treatment would consist of less drugs being prescribed concomitantly (Fig. ): whereas only 24.1% of patients had received pharmacological monotherapy in the old regimen, 41.3% of patients would receive only one drug after physicians had filled out the LANSS questionnaire. New monotherapy would consist mainly of AED (23.0%), followed by paracetamol (4.8%). Treatment strategies before and after applying the LANSS pain scale are illustrated in Fig. (n = 930). Only about half of the patients who previously received a pharmacological agent (paracetamol, NSAID/COX-2 inhibitors, opioids, antidepressive agents, or AED) would continue to receive the same drug in the future (Fig. ). In contrast, 23.5% of patients would receive AED for the very first time (180 out of 765 AED-naive patients).
Figure 4 Current and future drug treatments. Past and future treatment : proportion of patients taking only one drug who (1) will continue this treatment, (2) stop taking it, (3) who were not taking it but will start this treatment (4) who were not taking it and (more ...)