Effectiveness of Multimodal Treatment Strategies for Neuropathic Pain: A Retrospective Study from a Moroccan Rheumatology Centre

doi:10.21203/rs.3.rs-6936946/v1

Background: Neuropathic pain (NP) is a common and challenging clinical entity in rheumatology, necessitating an integrated therapeutic approach. Despite established guidelines, real-world data on multimodal management strategies in North African rheumatology settings remain scarce.

Methods: This retrospective study included patients with neuropathic pain (NP) who were treated at the Rheumatology Department of Ibn Rochd University Hospital, Casablanca, between October 2020 and April 2022. Inclusion was based on a DN4 score of ≥4. Both pharmacological and non-pharmacological treatment modalities were assessed. Outcome measures comprised pain intensity (VAS), sleep quality, functional status, and emotional well-being, as evaluated by the Hospital Anxiety and Depression Scale (HADS).

Results: The most frequently prescribed medications were pregabalin (52%), amitriptyline (36%), tramadol (22%), gabapentin (4.4%), and duloxetine (2%). A significant improvement in pain (VAS <3/10), sleep, and functional status was observed. Non-pharmacological approaches (physical therapy, TENS, and infiltrations) were implemented in 40% of patients and resulted in functional and emotional benefits. Etiological surgery was performed in 6.5% of cases and led to significant clinical improvement.

Conclusion: This study highlights the effectiveness of a multimodal, patient-centred approach in managing NP within a rheumatologic context. Integration of pharmacological and non-pharmacological modalities contributed to comprehensive clinical improvement, supporting the biopsychosocial model in chronic pain management.

Anesthesiology & Pain Medicine

Neuropathic pain

Multimodal treatment

Non-pharmacological therapy

Retrospective study

Quality of life

Rheumatology

Neuropathic pain (NP) is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” (1). It represents a significant public health burden, affecting up to 10% of the general population, and is often underdiagnosed and undertreated due to its complex and heterogeneous clinical presentations (2, 3). In rheumatology, NP frequently overlaps with nociceptive mechanisms, complicating both diagnosis and management (4).

The management of NP remains challenging, requiring a multimodal approach that addresses not only the sensory symptoms but also the emotional and functional impairments commonly associated with chronic pain (5). International guidelines recommend first-line pharmacological treatments such as tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoids (6). However, therapeutic responses are often partial, necessitating the integration of non-pharmacological strategies including physical therapy, transcutaneous electrical nerve stimulation (TENS), and cognitive-behavioral interventions (7, 8).

Despite these therapeutic advances, data on the real-world application of multimodal strategies for NP in rheumatological practice, particularly in North African populations, are limited. This study aimed to evaluate the real-life effectiveness of pharmacological and non-pharmacological treatments for neuropathic pain in a large Moroccan rheumatologic cohort.

1. Study Design and Setting

We conducted a retrospective and descriptive analysis over a 19-month period (October 2020 to April 2022) in the Department of Rheumatology at Ibn Rochd University Hospital Center, Casablanca.

2. Inclusion Criteria

Patients were eligible for inclusion if they presented with chronic pain of neuropathic origin, defined by a DN4 score ≥ 4. All included patients had received either pharmacological treatment, non-pharmacological therapy, or a combination thereof.

3. Data Collection

Data were extracted from medical records and included sociodemographic characteristics, comorbidities, duration and intensity of pain, and details of the treatment received. Treatment modalities were classified as pharmacological (e.g., pregabalin, amitriptyline, tramadol, gabapentin, duloxetine) or non-pharmacological (e.g., corticosteroid injections, physical therapy, TENS, cryotherapy).

4. Outcome Measures

Pain intensity, sleep quality and functional capacity were assessed using the Visual Analogue Scale (VAS). Emotional status was evaluated using the validated Arabic version of the Hospital Anxiety and Depression Scale (HADS). These parameters were assessed before and after treatment.

5. Statistical analysis

Data were analyzed using Jamovi software. Quantitative variables were expressed as means ± standard deviations and compared using the paired Student’s t-test. Categorical variables were presented as frequencies and percentages and analyzed using the chi-square (χ²) test. A p-value < 0.05 was considered statistically significant.

1. Sociodemographic Characteristics

Out of 7640 participants experiencing chronic pain, 1528 exhibited a DN4 score ⩾ 4, indicating a prevalence of neuropathic pain at 20%. The mean age was 57.3 ± 13.3 years, with a marked female predominance (90.6%). Approximately two-thirds of participants were married, and 90% resided in urban areas. A monthly income below 4000 MAD was reported by 83% of patients. The most common comorbidities were diabetes (26%), hypertension (30%), dysthyroidism (16%), and smoking (4%). Degenerative joint disease was noted in 57% of patients, and 22% had chronic inflammatory rheumatic diseases (Table 1).

Table 1

Socio-demographic characteristics of patients with neuropathic pain
Socio-demographic characteristics	Number (n)	Percentage (%)
Age (mean +/- SD years)	57.3 (+/-13.3)
≤ 45	306	20
> 45 et ≤ 60	544	36
> 60	669	44
Gender
Female	1385	91
Male	135	9
Sex ratio (F/M)	10:1
Marital status
Single	206	13.5
Married	1015	67
Divorced	95	6
Widowed	205	13.5
Education level
Illiterate	830	55
Primary	313	21
Secondary	219	14.5
Higher education	153	10
Occupation
Employed	130	9
Self-employed	160	11
Retired	82	5
Student	16	1
Unemployed	166	11
Housewife	957	63
Place of residence
Rural	156	10
Urban	1365	90
Monthly income (MAD)
≤ 4000	1159	83
> 4000	231	17
Comorbidities
Diabetes	392	26
Hypertension	460	30
Dysthyroidism	242	16
Smoking	59	4
Alcohol use	13	1
Chronic Rheumatic Disease	334	22
Degenerative disease	878	57
SD : Standard deviation

2. Clinical Features of Neuropathic Pain

The average DN4 score across the cohort was 5.27 ± 1.24 (range: 4 to 9), with a median of 5. The mean pain intensity on the VAS was 6.8. Moderate pain was reported by 56% of patients, while 36% described their pain as severe. Pain duration varied widely, with a mean of 41 months; 25% of patients had experienced pain for more than three months. NP was frequently associated with nociceptive components (70%), predominantly due to degenerative disorders.

3. Therapeutic Strategies

Pharmacological Management

Pregabalin was the most prescribed drug (52%; mean dose 156 mg/day), followed by amitriptyline (36%; 13 mg/day), tramadol with or without paracetamol (22%; 119 mg/day), gabapentin (4.4%; 468 mg/day), and duloxetine (2%). Combination therapy was required in 9% due to monotherapy inefficacy. The mean duration of pharmacological treatment was 9 months, with pregabalin and amitriptyline used continuously for 14.5 and 12 months, respectively.

Over 90% of patients initially had VAS pain scores > 3/10. Improvement was significant in patients treated with pregabalin (43%) or combination therapy (46%), with post-treatment VAS scores < 3/10. Sleep quality improved substantially, especially in patients receiving amitriptyline or gabapentin, among whom over 85% reported pain-related sleep disturbances before treatment. Functional limitations were initially reported in over 70% of cases. Post-treatment recovery was complete in 69% of those on pregabalin and 57% on combination therapy. All therapeutic regimens significantly improved emotional state, as assessed by HADS. Local treatments included corticosteroid injections (13.5%), lidocaine patches (1%), and capsaicin (Table 2).

Table 2

Effectiveness of Pharmacological Treatments on Pain, Function, Sleep, and Psychological Symptoms in Neuropathic Pain
Treatment	Before treatment mean (± SD)	After treatment mean (± SD)	p-value
Amitriptyline
Pain	7.23 ± 0.97	3.32 ± 1.39	0.001
Sleep	5.01 ± 2.51	1.63 ± 2.45	0.001
Function	5.75 ± 3.25	2.19 ± 2.14	0.001
Anxiety (HAD)	4.26 ± 2.82	2.98 ± 2.43	0.001
Depression (HAD)	3.03 ± 2.86	2.16 ± 2.37	0.001
Pregabalin
Pain	7.31 ± 0.75	2.22 ± 1.12	0.000
Sleep	4.57 ± 2.73	1.62 ± 2.45	0.000
Function	5.90 ± 3.18	2.14 ± 2.13	0.000
Anxiety (HAD)	4.27 ± 2.81	2.72 ± 2.29	0.000
Depression (HAD)	3.12 ± 2.88	2.06 ± 2.25	0.000
Gabapentin
Pain	6.99 ± 1.01	3.25 ± 1.80	0.000
Sleep	5.93 ± 2.23	2.67 ± 3.04	0.000
Function	6.69 ± 2.30	2.72 ± 2.22	0.000
Anxiety (HAD)	4.78 ± 3.10	3.31 ± 2.77	0.000
Depression (HAD)	2.93 ± 3.19	1.98 ± 2.33	0.0015
Duloxetine
Pain	7.09 ± 1.01	3.33 ± 2.10	0.000
Sleep	6.00 ± 2.41	3.15 ± 2.87	0.000
Function	6.85 ± 2.00	2.91 ± 2.40	0.000
Anxiety (HAD)	5.00 ± 3.15	3.88 ± 2.74	0.002
Depression (HAD)	3.67 ± 3.37	2.70 ± 3.03	0.005
Combination therapy
Pain	7.19 ± 0.98	3.03 ± 1.50	0.001
Sleep	5.43 ± 2.32	1.37 ± 2.42	0.001
Function	2.25 ± 0.72	1.83 ± 2.18	0.777
Anxiety (HAD)	4.71 ± 3.33	2.52 ± 2.48	0.001
Depression (HAD)	3.33 ± 3.54	1.86 ± 2.49	0.001
Tramadol
Pain	7.25 ± 0.97	3.43 ± 1.25	0.001
Sleep	4.66 ± 2.94	3.04 ± 2.73	0.001
Function	5.47 ± 3.34	3.36 ± 1.28	0.001
Anxiety (HAD)	5.59 ± 2.64	4.75 ± 2.56	0.001
Depression (HAD)	4.39 ± 3.14	3.76 ± 2.86	0.916
Local Treatment
Pain	7.48 ± 0.88	1.86 ± 1.55	0.001
Sleep	4.60 ± 2.53	0.77 ± 1.85	0.010
Function	5.43 ± 3.48	0.60 ± 1.45	0.000
Anxiety (HAD)	4.85 ± 2.35	2.70 ± 2.24	0.000
Depression (HAD)	4.08 ± 2.80	1.98 ± 1.89	0.000

Non-Pharmacological Therapies

Non-pharmacological techniques such as TENS (15.2%), O2CO2 therapy (1%), magnetotherapy (0.3%), cryotherapy (1%), and physical rehabilitation (24.5%) were employed to improve quality of life. All patients receiving these interventions had also received systemic pharmacological treatment. Non-pharmacological treatment was used in 40% of patients and significantly improved VAS scores and quality of life (Table 3). Initial VAS scores exceeded 3/10 in all patients. HADS anxiety and depression scores also improved significantly post-treatment.

Table 3

Clinical Impact of Non-Pharmacological and Surgical Interventions on Neuropathic Pain
Treatment	Before treatment mean (± SD)	After treatment mean (± SD)	p-value
TENS
Pain	7.32 ± 0.95	3.04 ± 1.26	0.000
Sleep	4.93 ± 2.70	1.64 ± 2.50	0.000
Function	6.02 ± 2.99	1.84 ± 2.14	0.000
Anxiety (HAD)	4.08 ± 2.62	3.25 ± 2.23	0.000
Depression (HAD)	3.86 ± 2.94	2.54 ± 2.30
Magnetotherapy
Pain	7.60 ± 0.89	3.20 ± 1.10	0.000
Sleep	4.00 ± 2.24	2.00 ± 2.74	0.000
Function	8.00 ± 0.00	3.20 ± 1.79	0.000
Anxiety (HAD)	3.50 ± 2.52	3.00 ± 1.41	0.809
Depression (HAD)	1.00 ± 0.00	0.00 ± 0.00	0.352
O2CO therapy
Pain	7.43 ± 0.93	2.62 ± 0.96	0.000
Sleep	4.00 ± 2.83	0.76 ± 1.88	0.000
Function	6.71 ± 2.89	1.23 ± 1.92	0.000
Anxiety (HAD)	2.82 ± 3.31	1.80 ± 2.53	0.063
Depression (HAD)	0.77 ± 1.72	1.00 ± 1.73	0.052
Cryotherapy
Pain	6.80 ± 1.01	3.14 ± 1.71	0.000
Sleep	5.73 ± 2.74	2.00 ± 2.88	0.000
Function	6.93 ± 1.03	2.57 ± 2.41	0.000
Anxiety (HAD)	3.87 ± 3.44	1.92 ± 1.98	0.010
Depression (HAD)	2.79 ± 3.29	2.20 ± 2.74	0.383
Physical therapy
Pain	7.43 ± 0.90	2.78 ± 1.10	0.001
Sleep	3.91 ± 2.85	1.08 ± 2.14	0.001
Function	5.79 ± 3.33	1.59 ± 2.03	0.001
Anxiety (HAD)	4.29 ± 2.85	2.45 ± 2.37	0.161
Depression (HAD)	3.36 ± 3.03	2.33 ± 2.46	0.383
Surgery
Pain	6.88 ± 0.99	2.74 ± 1.05	0.000
Sleep	5.93 ± 2.30	1.12 ± 2.21	0.000
Function	6.81 ± 1.58	0.96 ± 1.80	0.000
Anxiety (HAD)	5.69 ± 2.98	2.13 ± 1.84	0.000
Depression (HAD)	4.92 ± 3.22	1.87 ± 2.22	0.000

Surgical Management

Etiological surgery was performed in 6.5% of patients. Before surgery, 98% had VAS scores > 3/10, which improved in 65% postoperatively. Sleep disturbances were present in 92% and resolved in 79% post-surgery. Functional limitations were reported in 95% of cases and fully resolved in 77% following surgery. Psychological well-being improved significantly, as reflected by postoperative HADS scores (Table 3).

Neuropathic pain presents a major clinical challenge due to its complex pathophysiology and heterogeneous manifestations. It frequently coexists with nociceptive pain in rheumatologic conditions, often leading to underrecognition and inadequate treatment (1, 2). In our study, a high prevalence of NP was observed among patients with chronic musculoskeletal disorders, necessitating an integrated therapeutic strategy.

According to international recommendations from the European Federation of Neurological Societies (EFNS) and the Neuropathic Pain Special Interest Group (NeuPSIG), first-line treatments for NP include tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and gabapentinoids such as pregabalin and gabapentin (3, 6). Our results are consistent with these guidelines, demonstrating significant improvement in pain (VAS), sleep, emotional status, and functional capacity in patients receiving pregabalin and amitriptyline.

Pregabalin was the most frequently prescribed drug in our cohort, with marked improvements in pain, sleep, and anxiety—findings supported by previous studies (9–11). Gabapentin, although less used, was particularly effective in restoring sleep quality, corroborating results from randomized controlled trials and meta-analyses (12, 13). Tramadol, used in moderate pain, showed modest benefit, aligning with its classification as a second-line agent (8).

Amitriptyline provided measurable benefits on both pain and emotional scores. Despite its anticholinergic profile and sedative properties, TCAs remain among the most effective drugs for NP (5, 7). Duloxetine, used in diabetic neuropathy and fibromyalgia, was less frequently prescribed but remains a validated option (14, 15).

The combination of therapies proved superior in some cases, particularly when pain was refractory. Multimodal pharmacologic strategies are supported by studies showing additive effects and improved tolerability (16, 17).

Non-pharmacological approaches were used in 40% of cases and led to significant functional and emotional improvement. These included physical therapy, TENS, cryotherapy, and corticosteroid infiltrations. The role of physiotherapy in NP has been increasingly recognized, particularly in musculoskeletal conditions, due to its effects on pain modulation and mobility restoration (18, 19).

Sleep disturbances are highly prevalent in NP and contribute to reduced quality of life. The strong improvement in sleep across all treatment modalities in our study emphasizes the need to address this dimension in clinical management (20).

Moreover, the emotional burden of NP was confirmed through high baseline HADS scores. Anxiety and depression are known comorbidities in chronic pain syndromes and should be systematically screened and managed (6, 8, 21). Our findings support the integration of psychological assessment tools such as HADS in routine practice.

Surgical intervention, though limited to 6.5% of patients, showed significant benefits, particularly in patients with compressive neuropathies. This aligns with evidence suggesting that surgery remains an effective etiological treatment when indicated (11).

Overall, our study demonstrates that a multimodal and biopsychosocial approach to NP results in global clinical improvement. It reinforces the current paradigm shift from symptom-based to mechanism-based pain management (22–24).

Our findings contribute valuable insights into the real-life management of NP in a Moroccan rheumatology setting, reinforcing the effectiveness of a multimodal approach. However, several limitations must be acknowledged, including the retrospective design, potential information bias from medical records, and the absence of a control group.

Future prospective studies should explore the long-term impact of integrated care models and validate the role of non-pharmacological therapies in broader populations.

Our study demonstrates the clinical value of a multimodal approach to managing neuropathic pain in a rheumatological setting. Pharmacological therapies, particularly pregabalin and tricyclic antidepressants, yielded substantial improvements in pain intensity, sleep quality, functional status, and emotional health. The adjunctive use of non-pharmacological and surgical interventions further enhanced patient outcomes. These findings advocate for the integration of biopsychosocial principles into routine care and support the development of personalised treatment strategies for chronic pain management. Further research is warranted to validate these results across diverse settings and explore long-term outcomes.

This retrospective study was conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Ethical approval was obtained from the local Ethics Committee of Ibn Rochd University Hospital.

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The authors declare no competing interests.

Effectiveness of Multimodal Treatment Strategies for Neuropathic Pain: A Retrospective Study from a Moroccan Rheumatology Centre

Status:

Version 1

Abstract

Introduction

Material and methods

1. Study Design and Setting

2. Inclusion Criteria

3. Data Collection

4. Outcome Measures

5. Statistical analysis

Results

1. Sociodemographic Characteristics

2. Clinical Features of Neuropathic Pain

3. Therapeutic Strategies

Pharmacological Management

Non-Pharmacological Therapies

Surgical Management

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1