Pain Research and Treatment

Pain Research and Treatment / 2014 / Article

Research Article | Open Access

Volume 2014 |Article ID 518716 | https://doi.org/10.1155/2014/518716

José de Andrés, José-Luis de la Calle, María Pérez, Vanessa López, "Clinical Characteristics, Patient-Reported Outcomes, and Previous Therapeutic Management of Patients with Uncontrolled Neuropathic Pain Referred to Pain Clinics", Pain Research and Treatment, vol. 2014, Article ID 518716, 15 pages, 2014. https://doi.org/10.1155/2014/518716

Clinical Characteristics, Patient-Reported Outcomes, and Previous Therapeutic Management of Patients with Uncontrolled Neuropathic Pain Referred to Pain Clinics

Academic Editor: Robert L. Barkin
Received26 Sep 2013
Revised07 Apr 2014
Accepted07 Apr 2014
Published05 May 2014

Abstract

Background. The aim of this report was to evaluate the clinical profile and previous management of patients with uncontrolled neuropathic pain who were referred to pain clinics. Methods. We included adult patients with uncontrolled pain who had a score of in the DN4 questionnaire. In addition to sociodemographic and clinical data, we evaluated pain levels using a visual analog scale as well as anxiety, depression, sleep, disability, and treatment satisfaction employing validated tools. Results. A total of 755 patients were included in the study. The patients were predominantly referred to pain clinics by traumatologists (34.3%) and primary care physicians (16.7%). The most common diagnoses were radiculopathy (43%) and pain of oncological origin (14.3%). The major cause for uncontrolled pain was suboptimal treatment (88%). Fifty-three percent of the patients were depressed, 43% had clinical anxiety, 50% rated their overall health as bad or very bad, and 45% noted that their disease was severely or extremely interfering with their daily activities. Conclusions. Our results showed that uncontrolled neuropathic pain is a common phenomenon among the specialties that address these clinical entities and, regardless of its etiology, uncontrolled pain is associated with a dramatic impact on patient well-being.

1. Introduction

Neuropathic pain is defined as pain that originates from a lesion or disease that affects the somatosensory pathways within the peripheral or central nervous system [1]. Neuropathic pain is common among the general population, with prevalence rates of 7-8% [2, 3]. Neuropathic pain, which is also a common occurrence (12%) among patients who are managed by primary care physicians [4], accounts for a high proportion (20%) of the patients who are referred to specialized pain units [5]. The causes of neuropathic pain comprise a wide and heterogeneous number of clinical conditions, such as diabetic neuropathy, complex regional pain syndrome, spinal cord injury pain, postherpetic neuralgia, postoperative pain, trigeminal neuralgia, drug-induced polyneuropathies, HIV-associated neuropathy, multiple sclerosis, and central pain syndromes secondary to vascular lesions [6, 7]. Although it may be acute in nature, in the vast majority of patients, neuropathic pain is a chronic condition. Regardless of its etiology, neuropathic pain is disabling and substantially impairs patients’ health-related quality of life [812]. This condition is associated with high societal costs because of the patients’ loss of productivity and increased utilization of health resources [8, 10, 1315].

Managing neuropathic pain requires an interdisciplinary approach in which pharmacological treatment is fundamental [5, 16]. Despite the availability of several effective drugs, neuropathic pain treatment is challenging: response to treatment is unpredictable; despite the fact that the patients may receive several drugs for pain treatment, moderate-to-severe levels of pain are common; suboptimal treatment is also common with patients who receive ineffective treatments, such as nonsteroidal anti-inflammatory drugs or lower-than-recommended doses of the prescribed treatment; and delayed referral to pain clinics is also common [4, 8, 1618].

Although there is consensus that many patients with neuropathic pain do not respond adequately or are unable to tolerate existing treatments [19, 20], epidemiologic information about this population is limited [21]. The aim of this report was to evaluate the clinical profile and previous management of patients with uncontrolled neuropathic pain who were referred to pain clinics.

2. Patients and Methods

2.1. Study Design, Setting, and Patients

This report was an observational, multicenter, and prospective study performed by 161 investigators from pain clinics throughout Spain between February 2009 and February 2010. The study was approved by the Ethics Committee of the Hospital General Universitario de Valencia (Spain). Written informed consent was obtained from every subject. The study was conducted in accordance with the principles of the Declaration of Helsinki. In this report, we presented the baseline (cross-sectional) data of the study.

For inclusion in the study, the patients had to fulfill the following criteria: age 18 years or older; referral to a pain clinic because of uncontrolled pain; and a score of equal to or greater than 4 in the DN4 questionnaire. The patients were excluded from the study if they were unable to understand the study objectives or complete the self-administered questionnaires.

2.2. Study Assessments

At baseline, the following information was recorded: sociodemographic data, type of specialist referring the patient, diagnostic confirmation of neuropathic pain, confirmation of the presence of uncontrolled pain as assessed by the investigator, etiology and duration of pain, causes for uncontrolled pain, pain intensity as measured using a 0 to 100 mm visual analog scale (VAS), and signs and symptoms of neuropathic pain. We also recorded pharmacological and nonpharmacological treatment for neuropathic pain. Additionally, the Spanish validated versions of the following questionnaires and scales were completed: DN4 questionnaire, Hospital and Anxiety Depression Scale (HADS), the Medical Outcomes Study Sleep (MOS Sleep) Scale, the World Health Organization Disability Assessment Schedule (WHO-DAS II), and the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q).

The neuropathic pain diagnostic questionnaire DN4 consists of 10 items that describe different pain characteristics. A score of at least 4 of 10 possible points is considered acceptable to identify neuropathic pain with 83% sensitivity and 90% specificity [2224].

The HADS, which is a self-administered instrument, consists of 14 items: 7 items that refer to depression symptoms and 7 items that refer to anxiety symptoms [25, 26]. Each item score ranges from 0 to 3, where 0 represents the absence of that symptom and 3 represents the highest severity or frequency of the symptom. By adding the 7 items of each subscale, two scores ranging from 0 to 21 are obtained that represent depression and anxiety (HADS-D and HADS-A), respectively.

The MOS Sleep Scale, a self-administered questionnaire, evaluates the key aspects of sleep [27, 28] and consists of 12 items that comprise six subscales or domains: sleep disturbances, snoring, shortness of breath or headache upon awakening, adequacy of sleep, day somnolence, and amount of sleep. Additionally, the MOS Sleep Scale provides a summary index of sleep disturbances that can be obtained from 9 of its items; the higher the score is, the worse the sleep is, with the exception of amount of sleep and adequacy of sleep dimensions, which are scored in the opposite direction. In patients with neuropathic pain, this scale has shown to have appropriate psychometric properties [28].

The WHO-DAS II comprises 12 items that evaluate an individual’s level of functioning and disability in six areas: understanding and communicating, getting around, self-care, getting along with people, life activities, and participation in society [2931]. The patients are required to answer questions regarding how many difficulties they experienced in the last 30 days as a result of their health condition, using a five-point scale from 1 (none) to 5 (extreme difficulty or cannot do it). The raw scores are transformed into a standard scale that ranges from 0 to 100; the higher scores reflect more severe disability. A global score is obtained that ranges from 0 to 700 (if work activities outside the home are assessed) or from 0 to 600.

The SATMED-Q, a self-administered questionnaire, consists of 17 items that evaluate six dimensions: treatment effectiveness, convenience of use, impact on daily activities, medical care, global satisfaction, and undesirable side-effects [32, 33]. The questionnaire also provides a global score for satisfaction with drug treatment by summing the scores of all of the domains. The raw scores are transformed into a scale that ranges from 0 to 100; the higher scores indicate greater satisfaction. Questions on medication side-effects include whether the patient experienced side-effects and whether the side-effects interfered with their physical exercises, leisure time, and daily activities.

2.3. Statistical Analysis

The analysis was essentially descriptive using the means and standard deviations for quantitative variables and using the absolute and relative frequencies for qualitative variables. The patients were categorized as having clinical anxiety or depression if they had a score equal or greater than 11 in the anxiety or depression subscales of the HAD.

3. Results

We included 755 patients in the study. We excluded 27 (3.6%) patients who did not meet the selection criteria, thereby leaving 728 evaluable patients.

3.1. General Characteristics of Patients

The patients had a mean age of 57 years, were predominantly women (61%), and exhibited obesity in a high proportion (20%) (Table 1). More than one-third of the patients were referred to pain clinics by traumatologists, followed by those who were referred by primary care physicians (Figure 1).


CharacteristicOverall Primary care Traumatology Neurology Neurosurgery Rehabilitation Rheumatology Other surgeries Other specialties

Age, mean ± SD 13.1
Sex (female), %60.656.365.860.763.051.478.159.751.0
BMI, %
 Underweight 1.60.01.58.50.03.06.90.0 0.0
 Normal34.431.831.236.236.439.427.643.1 40.2
 Overweight   Obesity I 43.9 51.4 43.7 38.3 47.7 36.4 41.4 37.3 45.1
  Obesity II16.715.019.612.811.418.217.217.611.0
  Obesity III2.10.92.54.32.30.03.42.02.4
  Obesity IV1.30.91.50.02.33.03.40.01.2

BMI: body mass index; SD: standard deviation.

3.2. Pain Characteristics and Treatment

The patients had severe pain with a mean score of 75 using the VAS; the duration of pain was generally 2,6 years and was longer for those patients who were referred to pain clinics from the departments of rheumatology, neurosurgery, and neurology (Table 2). The majority (43%) of the patients were diagnosed with radiculopathy (Figure 1), which was the predominant diagnosis among those patients referred by traumatology, neurosurgery, rheumatology, and rehabilitation departments (Table 2). The patients who were referred by neurologists had trigeminal neuralgia and central neuropathic pain as their primary diagnoses, whereas primary care physicians referred patients with oncological pain or radiculopathy. The type, spontaneous or evoked, and subtypes of pain by clinical entity are presented in Table 3. All subtypes of spontaneous pain were present in more than 80% of the patients, regardless of the clinical entity. The subtypes of evoked pain were less represented, especially thermal allodynia; however, nearly every subtype was present in more than two-thirds of the patients in every clinical entity.


CharacteristicOverall Primary care Traumatology Neurology Neurosurgery Rehabilitation Rheumatology Other surgeries Other specialties

DN4 (0–10), mean ± SD
VAS, mean ± SD
Duration of pain (yrs), mean ± SD
Causes for uncontrolled pain, %
Misdiagnosis11.111.912.83.65.212.79.416.18.3
Nonoptimized treatment87.682.293.482.187.983.390.688.783.3
 Use of ineffective drugs45.845.950.428.337.346.741.452.744.3
 Subtherapeutic dose45.748.546.047.843.156.541.430.950.0
 Other25.318.623.537.039.220.024.721.831.0
Lack of compliance7.25.15.912.55.211.115.64.86.2
Intolerance6.69.33.316.16.92.89.43.27.8
Other7.38.59.810.76.911.13.18.14.1
Causes of neuropathic pain, %
Neuropathy
 Diabetic3.810.40.95.80.02.80.03.56.1
 Other3.20.90.95.81.82.89.48.80.0
Neuralgia
 Trigeminal4.67.00.425.05.50.04.25.30.0
 Other3.52.62.17.73.62.83.33.18.8
Radiculopathy43.132.567.011.563.652.863.38.33.5
Nerve entrapment syndrome5.64.42.10.05.52.816.71.89.4
Plexopathy3.53.53.93.80.05.23.31.82.8
Complex regional pain syndrome5.20.98.65.83.616.73.31.81.0
Postsurgery/trauma7.83.53.01.95.52.83.311.545.6
Malignant/radiation/chemotherapy-induced pain14.336.01.311.55.50.03.341.78.8
Central neuropathic pain3.00.91.317.35.511.10.01.00.0
Other neuropathic pains2.51.81.33.80.02.13.310.52.8

DN4: neuropathic pain diagnostic questionnaire; SD: standard deviation; VAS: visual analog scale; Yrs: years.

CharacteristicDiabetic neuropathy Other neuropathies Trigeminal neuralgia Other neuralgia Radiculopathy Nerve entrapment syndrome Plexopathy Complex regional pain syndrome Postsurgery/trauma Oncological pain Central neuropathic pain

Spontaneous pain, %
 Lancinating98.089.596.6100.060.191.281.087.590.990.490.0
 Burning100.090.095.792.687.097.182.796.989.992.590.0
 Paraesthesias100.095.086.282.696.897.190.993.793.390.290.5
 Dysaesthesias100.095.089.391.392.894.195.5100.095.594.485.0
Evoked pain, %
 Static allodynia95.890.091.588.368.773.554.593.684.882.080.0
 Dynamic allodynia91.795.086.278.369.670.654.5100.093.583.785.0
 Thermal allodynia70.860.085.268.252.061.845.578.165.971.575.0
 Mechanical hyperalgesia84.085.089.378.381.273.577.390.686.786.871.4
 Hyperpathia83.370.077.869.670.363.672.784.476.777.573.7

The major cause for uncontrolled pain, as assessed by the pain clinic investigators, was attributed to suboptimal treatment (88%) because of the use of ineffective drugs or subtherapeutic doses (Table 2). The use of ineffective drugs was less common among the patients who were referred by the neurology and neurosurgery departments.

The patients were receiving a mean of 3 drugs; one-third of the patients, regardless of the referral specialty, were receiving 4 or more drugs (Table 4). The most common prescribed drugs were antiepileptics (54%), opiods (40%), and nonsteroidal anti-inflammatory agents (40%); the latter drugs were more commonly prescribed by specialists in rehabilitation facilities (55%), rheumatologists (50%), and traumatologists (46%) and were less commonly prescribed by neurologists (28%) and primary care physicians (34%). Table 5 shows the doses and treatment duration of the most common drugs that patients were receiving at the time of referral.


CharacteristicOverall Primary care Traumatology Neurology Neurosurgery Rehabilitation Rheumatology Other surgeries Other specialties

Number of previous treatments
Mean ± SD
 1, %11.915.512.75.65.89.13.317.610.9
 2, %27.423.624.927.828.827.343.335.331.5
 3, %25.629.124.927.830.827.320.021.627.2
 >4, %35.131.837.638.934.636.433.325.530.4
Treatment at the time of inclusion, %
Paracetamol25.019.133.913.015.418.226.725.522.8
NSAIDs40.133.647.527.836.554.550.043.125.0
Opiods39.641.840.338.955.833.353.317.635.9
 Tramadol29.528.229.429.648.124.243.313.728.3
 Others14.816.414.918.515.49.16.77.815.2
AED54.156.448.481.569.248.543.341.256.5
 Pragabalin26.721.829.433.328.824.223.323.525.0
 Gabapentin23.528.219.031.534.615.210.017.630.4
 Carbamazepine/oxcarbazepine6.39.10.531.53.86.13.33.95.4
 Other4.42.73.27.411.56.16.70.05.4
Antidepressants19.724.515.831.517.39.120.017.625.0
 Duloxetine5.35.55.41.95.83.010.03.96.5
 Tricyclics11.313.66.325.911.56.16.711.817.4
 Other4.25.54.15.61.93.010.02.03.3
Other drugs47.647.346.651.934.639.446.751.054.3
Nonpharmacological52.046.458.844.451.981.853.347.139.1

AED: antiepileptic drugs: NSAIDs: nonsteroidal anti-inflammatory drugs; SD: standard deviation.

Drug% patientsMean dose (SD) mg/dayDuration (months) mean (SD)

Paracetamol21.22,398.6 (960.1)5.5 (6.3)
NSAIDs
 Ibuprofen17.91,428.4 (457.2)8.5 (13.3)
 Metamizol14.82,158.8 (1,598.7)8.5 (13.3)
 Diclofenac6.3124.9 (34.8)8.5 (13.3)
Opiods
 Tramadol27.1182.9 (110.1)12.1 (21.5)
 Fentanil8.618.5 (25.1)7.5 (12.9)
AED
 Pragabalin27.2244.6 (242.5)13.8 (17.4)
 Gabapentin19.01,297.7 (646.9)9.3 (12.0)
 Carbamazepine5.1577.1 (313.5)22.2 (27.5)
Antidepressants
 Amitriptyline10.836.2 (27.3)12.9 (15.4)
 Duloxetine6.158.3 (22.0)8.1 (8.0)
Other drugs
 Clonazepam5.72.1 (2.7)2.2 (1.0)

SD: standard deviation.

Patients with uncontrolled pain showed low satisfaction with their treatment with a global satisfaction score of 44 of 100. Treatment effectiveness and the impact of medicine on their everyday life were the areas exhibiting lower satisfaction, with mean scores of 32 and 30, respectively (Table 6).


CharacteristicOverall Primary care Traumatology Neurology Neurosurgery Rehabilitation Rheumatology Other surgeries Other specialties

Experiencing side effects, %51.757.849.367.951.947.160.037.346.3
SATMED-Q dimensions, mean ± SD
 Undesirable side effects
 Treatment effectiveness
 Convenience of use
 Impact on daily living/activities
 Medical care
 Global satisfaction
Total composite score

SATMED-Q: Treatment Satisfaction with Medicines Questionnaire; SD: standard deviation.

The number of drugs that the patients were receiving was higher among the patients with central neuropathic pain (3.7), plexopathy (3.5), radiculopathy (3.3), and complex regional pain syndrome (3.2) and was lower among those with diabetic neuropathy (2.3) (Table 7). The use of antiepileptics, especially carbamazepine and oxcarbazepine, was higher in patients with trigeminal neuralgia (90.6%); the use of opioids was higher in patients with plexopathy (50%), nerve entrapment syndrome (46%), and radiculopathy (45%). Approximately 50% of the patients with radiculopathy, nerve entrapment syndrome, or complex regional syndrome were receiving NSAIDs. Suboptimal treatment was the major cause for uncontrolled pain, regardless of the clinical entity, but was overrepresented in patients with plexopathy (96%) and in patients with radiculopathy (91%) (Table 7). Overall, the treatment satisfaction was low, and the satisfaction with treatment efficacy was equally low (Table 7).


CharacteristicDiabetic neuropathy Other neuropathies Trigeminal neuralgia Other neuralgia Radiculopathy Nerve entrapment syndrome Plexopathy Complex regional pain syndrome Postsurgery/trauma Oncological pain Central neuropathic pain

VAS, mean ± SD
WHO-DAS II Interference with life (severe/extreme), %52.052.742.939.146.738.352.467.733.430.466.7
Number of previous treatments, mean ± SD
Treatment at the time of inclusion, %
Paracetamol17.45.66.323.832.028.622.720.025.520.910.0
NSAIDs17.433.321.947.649.648.640.948.644.722.010.0
Opiods34.827.828.123.844.945.750.037.127.731.950.0
 Tramadol21.722.228.114.333.534.345.525.714.924.235.0
 Others13.011.13.19.515.114.318.220.012.813.230.0
AED52.272.290.647.645.642.945.554.336.270.385.0
 Pragabalin26.138.925.014.328.314.327.331.419.124.235.0
 Gabapentin30.433.331.319.016.925.718.211.417.038.560.0
 Carbamazepine/ oxcarbazepine0.00.056.314.31.10.04.55.70.012.110.0
 Other4.35.612.50.02.62.90.05.70.06.620.0
Antidepressants17.422.218.819.016.214.345.528.614.923.120.0
 Duloxetine8.75.60.04.86.62.90.05.74.35.55.0
 Tricyclics8.722.215.69.55.98.631.820.08.516.55.0
 Other0.00.03.14.84.45.713.65.72.11.110.0
Other drugs34.844.443.852.450.037.140.937.144.748.455.0
Causes for uncontrolled pain, %
Misdiagnosis15.418.23.112.58.410.320.811.127.89.14.8
Nonoptimized treatment80.877.378.183.391.289.795.886.177.887.985.7
 Use of ineffective drugs61.929.420.045.048.757.139.148.469.036.811.1
 Subtherapeutic dose47.641.252.025.046.140.043.538.728.657.555.6
 Other9.541.244.040.024.417.130.425.819.021.850.0
Lack of compliance15.44.50.012.56.17.74.211.11.95.19.5
Intolerance0.09.112.54.27.75.14.22.83.76.119.0
Other11.59.112.54.26.40.00.05.67.410.19.5
SATMED-Q
Total score, mean ± SD
Efficacy, mean ± SD

AED: antiepileptic drugs; NSAIDs: nonsteroidal anti-inflammatory drugs; SATMED-Q: Treatment Satisfaction with Medicines Questionnaire; SD: standard deviation; VAS: visual analog scale; WHO-DAS II: World Health Organization Disability Assessment Schedule II; Yrs: years.
3.3. Impact of Uncontrolled Pain on Psychological Well-Being and Disability

More than half of the patients were diagnosed with depression, and 43% of the patients were diagnosed with anxiety (Table 8). Sleep was also deeply affected among these patients. The patients who were referred to pain clinics by rheumatologists exhibited symptoms that had the greatest impact on their psychological well-being and sleep (Table 8).


CharacteristicOverall
Primary care
Traumatology
Neurology
Neurosurgery
Rehabilitation
Rheumatology
Other surgeries
Other specialties

HADS-depression (0–21)
 mean ± SD
 Clinical depression, %53.048.155.053.853.852.971.441.554.8
HADS-anxiety (0–21)
 mean ± SD
 Clinical anxiety, %43.1%32.445.444.234.651.463.343.443.5
MOS-Sleep, mean ± SD
 Summary index (0–100)
 Sleep disturbance (0–100)
 Snoring (0–100)
 Shortness of breath (0–100)
 Adequacy of sleep (100–0)
 Amount of sleep, hours
 Daytime somnolence (0–100)

HADS: Hospital and Anxiety Depression Scale; MOS-Sleep: the Medical Outcomes Study Sleep Scale; SD: standard deviation.

The proportion of disability among patients with uncontrolled pain was high, with approximately 50% of the patients rating their overall health as bad or very bad and 45% noting that their disease was severely or extremely interfering with their life (Table 9). The difficulties were present most of the time (22 of 30 days) and prevented them from executing their daily activities 15 days a month. The most affected dimensions were life activities either at home or at work (Table 9).


CharacteristicOverall Primary care Traumatology Neurology Neurosurgery Rehabilitation Rheumatology Other surgeries Other specialties

WHO-DAS II H1-H5
 Overall health (Bad/very bad), %48.944.949.652.756.645.753.536.451.0
 Interference with life  (Severe/extreme), %45.336.349.351.047.044.150.031.546.8
 Duration of difficulties (days),  mean ± SD
 Days totally unable to carry out   usual activities/work, mean ± SD
 Days cutting back or reducing   usual activities/work
WHO-DAS II dimensions, mean ± SD
 Understanding and  communicating