Introduction
Sickle cell disease (SCD) comprises inherited hemoglobin disorders characterized by the presence of hemoglobin S, usually resulting from a pathogenic variant in the β-globin gene. Under conditions that promote deoxygenation, hemoglobin S polymerizes, altering erythrocyte shape and deformability. These changes contribute to hemolysis, vaso-occlusion, tissue ischemia, and acute pain.
Individuals with SCD may also experience persistent or recurrent chronic pain arising from disease-related complications and changes in pain processing.1
SCD represents a substantial global health burden, particularly in sub-Saharan Africa. The geographical distribution of hemoglobin S varies across populations, and population-level estimates have demonstrated a considerable burden in regions where access to screening, diagnostic services, specialist care, and comprehensive treatment remains uneven.2 In these settings, recurrent pain may be compounded by delayed presentation, limited access to essential medicines, transport costs, and interruptions in follow-up care.
Pain is among the most burdensome manifestations of SCD. Acute vaso-occlusive episodes may require urgent assessment and prompt analgesia, whereas chronic pain may persist between acute episodes and interfere with mobility, sleep, education, employment, emotional well-being, and social participation. Findings from the international Sickle Cell World Assessment Survey demonstrated the substantial effects of SCD symptoms on everyday functioning and disease management.3 Pain should therefore be assessed within a broader biopsychosocial framework that recognizes interactions among physiological processes, psychological responses, social circumstances, and the healthcare environment.
Pharmacological treatment, including opioids and non opioid analgesics, remains central to the management of SCD pain. Disease-modifying treatment and appropriate management of complications are also important components of comprehensive care. Nevertheless, adverse effects, incomplete pain relief, difficulties obtaining timely treatment, and the effects of recurrent pain on daily functioning have supported the investigation of complementary strategies.
Non pharmacological interventions may help patients develop coping skills, manage distress, improve self-efficacy, and participate more actively in their care. These interventions include cognitive behavioral therapy (CBT), biofeedback, relaxation, guided imagery, massage, yoga, virtual reality, and transcutaneous electrical nerve stimulation (TENS). Other approaches, such as mindfulness, acupuncture, hypnosis, and spiritual support, also warrant consideration, although the amount of direct evidence available for SCD varies substantially across these interventions.
In this review, the evidence was interpreted according to intervention type, clinical setting, population, and outcome. For example, a reduction in experimentally induced pain sensitivity was not considered sufficient evidence of a reduction in spontaneous vaso-occlusive pain, hospital attendance, or analgesic requirements. Similarly, findings from postoperative pain studies or studies involving other chronic pain populations were not assumed to apply directly to SCD.
Implementation presents additional challenges, particularly in low- and middle-income countries (LMICs). These include limited availability of trained psychologists and pain specialists, competing healthcare priorities, out-of-pocket costs, inadequate digital infrastructure, language barriers, and limited access to locally validated educational materials. In settings where access to essential analgesia is already constrained, complementary interventions should not be promoted as substitutes for appropriate clinical treatment.
This narrative review critically examined the evidence for selected non pharmacological interventions in SCD, distinguished direct evidence from indirect extrapolation, evaluated methodological limitations, and identified priorities for clinical practice and research, with particular attention to resource-constrained settings.
Methods
Review Design and Scope
This article was designed as a narrative review rather than a systematic review or meta-analysis. The review aimed to critically synthesize evidence on non pharmacological interventions for acute and chronic pain in SCD, explain differences in the strength of evidence among interventions, and discuss clinical and implementation implications.
Eligible evidence types included randomized controlled trials, quasi-experimental studies, observational studies, systematic reviews, scoping reviews, and relevant clinical practice guidelines. Original clinical studies involving people with SCD were prioritized when intervention effects were assessed. Systematic reviews and guidelines were used to contextualize findings, identify additional primary studies, and assess the overall certainty of the evidence.
Literature Search and Study Selection
The literature search was conducted using relevant biomedical and psychological databases, including MEDLINE/PubMed, Embase, Google Scholar, CINAHL, PsycINFO, and the Cochrane Library, where access was available. Searches covered the earliest available records through the final search date rather than being restricted to recent publications. Reference lists of relevant primary studies, systematic reviews, and clinical practice guidelines were also examined to identify older SCD-specific intervention studies.
The search strategy combined controlled vocabulary and free-text terms relating to SCD, pain, and non pharmacological interventions. The search structure for MEDLINE/PubMed included the following concepts:
Condition: “sickle cell disease,” “sickle cell anemia,” “hemoglobin S disease,” and relevant controlled vocabulary.
Pain: pain, pain management, vaso-occlusive crisis, pain episode, acute pain, chronic pain, pain intensity, and pain frequency.
Interventions: cognitive behavioral therapy, cognitive behavioural therapy, psychotherapy, coping skills, biofeedback, guided imagery, relaxation, massage, yoga, virtual reality, transcutaneous electrical nerve stimulation, TENS, acupuncture, mindfulness, hypnosis, meditation, and spiritual or religious coping.
Study identification: randomized controlled trial, clinical trial, controlled study, observational study, systematic review, and scoping review.
The final search combined the condition- and pain-related concepts with the intervention-related concepts. Studies without a clear pain-management outcome were used for background context only. The review included 13 listed records relevant to SCD, covering epidemiology, disease burden, pain-management guidelines, and pharmacological and nonpharmacological interventions.
Evidence Appraisal and Synthesis
The findings were organized by intervention category, clinical setting, age group, pain outcome, and study design. Particular attention was given to pain intensity, pain frequency, coping, analgesic consumption, functional interference, quality of life, healthcare utilization, intervention adherence, and adverse events.
The review distinguished statistical evidence of an intervention effect from the certainty that the finding was reliable and clinically applicable. Study design, sample size, comparator selection, attrition, outcome measurement, follow-up duration, and consistency across studies were considered when interpreting the findings.
Because interventions, populations, comparators, and outcomes varied, the findings were synthesized narratively rather than pooled quantitatively. No new pooled effect estimate or formal risk-of-bias assessment was undertaken. Where the available source reported a specific effect estimate, it was presented in context.
Where detailed study-level information could not be verified, conclusions were appropriately qualified.
Results and Discussion
Overview of the Evidence
The available literature showed that non pharmacological pain management in SCD had been investigated through psychological and behavioral interventions, physical and sensory techniques, and technology-assisted approaches. However, the evidence was unevenly distributed across interventions, with relatively few adequately powered controlled studies and substantial variation in study populations and outcomes.
The American Society of Hematology (ASH) 2020 guideline conditionally recommended massage, yoga, TENS, virtual reality, and guided audiovisual relaxation, in addition to standard pharmacological management, for children and adults seeking treatment for acute SCD pain. These recommendations were based on very-low-certainty evidence derived from both direct SCD studies and indirect evidence, particularly studies involving postoperative pain.4 The guideline therefore supported consideration of selected interventions as adjuncts but did not establish all of them as reliably effective treatments.
A systematic review by van Veelen et al examined non pharmacological interventions for pain in children and young people with SCD. The review included 10 articles comprising five randomized controlled trials and five quasi-experimental studies, involving 422 participants. The interventions included CBT, biofeedback, massage, virtual reality, and yoga.
The authors reported favorable findings for selected outcomes, particularly for CBT and biofeedback in outpatient settings and virtual reality and yoga in inpatient settings. However, heterogeneity in study design and outcome measurement prevented quantitative pooling and limited the certainty of the overall conclusions.5
A separate scoping review by Garrett et al examined non pharmacological interventions for sickle cell crisis in pediatrics. After screening 1,348 studies, 27 articles were included in a scoping review on non-pharmacological interventions for pediatric SCD patients managing pain during sickle cell crises (SCC). The interventions varied widely, with inconsistent effectiveness reported for virtual reality, guided imagery, and cognitive-behavioral approaches.
Common home interventions included prayer, massage, and distraction, while prayer and fluid intake were noted in hospital settings, though examined in few studies.6 The review concluded that many interventions remain unempirically validated, highlighting the need for further research on their effectiveness in alleviating SCC pain.6 Although these reviews provided useful overviews of the field, their conclusions were interpreted alongside the original clinical studies rather than as substitutes for primary evidence.
Taken together, the literature supported a differentiated interpretation of the available evidence. Some interventions had promising direct SCD-specific findings, whereas others had limited or inconsistent evidence. Several approaches remained insufficiently studied in SCD.
The following sections examine these distinctions by intervention category.
Psychological and Behavioral Interventions
Cognitive Behavioral Therapy
CBT addresses interactions among thoughts, emotions, behaviors, and pain experiences. Pain-focused CBT may include cognitive restructuring, relaxation, activity planning, coping skills, goal setting, and strategies for managing pain-related distress. The intervention does not imply that SCD pain is psychological in origin; rather, it aims to help patients respond to pain and its functional consequences.
Direct SCD-specific randomized and quasi-experimental study by van Veelen et al involved ten articles (five RCTs and five QED studies) with 422 participants. Out “of 1048 publications retrieved and screened by two investigators”, “children received one single training session in four studies”7. Compared with the control condition, the intervention increased coping attempts, reduced negative thinking, and lowered reported pain responses to calibrated laboratory stimuli.
These findings suggested that brief cognitive skills training could influence pain coping and experimental pain sensitivity in adults with SCD. However, laboratory pain sensitivity was not equivalent to a reduction in naturally occurring vaso-occlusive episodes, and the study did not establish that the intervention reduced hospitalization or long-term healthcare utilization.7
Anie et al investigated self-help, manual-assisted CBT for SCD.8 This study was relevant to the feasibility of structured behavioral interventions, including approaches that might reduce reliance on repeated face-to-face specialist appointments. Nevertheless, the findings required interpretation in relation to the study design, sample size, delivery method, comparison group, and outcomes measured.
More recent evidence was provided by the multicenter randomized controlled trial conducted by Palermo et al. The study evaluated I can Cope with Sickle Cell Disease, a digital CBT intervention, among adolescents aged 12–18 years. A total of 137 participants were enrolled, and 111 were included in the randomized analysis: 57 received the digital intervention and 54 received the education control.
At six months, the digital CBT group demonstrated a greater reduction in average pain intensity than the education group, with a reported treatment coefficient of −1.32 (95% confidence interval [CI], −2.29 to −0.34; P = 0.009). The intervention group also experienced fewer pain days, with an incidence rate ratio of 0.63 (P = 0.006).9
This trial provided comparatively strong direct evidence that a structured digital behavioral intervention improved selected pain outcomes among adolescents with SCD. However, the findings could not automatically be generalized to adults, all digital programs, acute inpatient pain, or settings without reliable device access and clinical support. Although digital delivery could reduce travel and scheduling burdens, it could also introduce barriers related to internet connectivity, device ownership, literacy, language, privacy, and sustained engagement.
In general, CBT emerged as one of the more promising non pharmacological approaches for SCD, particularly for pain coping and selected outcomes in pediatric and adolescent populations. Further research was needed to establish the durability of benefits, effectiveness in adults, implementation requirements, and effects on physical functioning and healthcare utilization.
Biofeedback
Biofeedback provides information about physiological processes, such as muscle tension, breathing, or heart rate, to help individuals recognize and modify physiological responses. It is sometimes combined with relaxation training and cognitive coping strategies.
Biofeedback had been investigated in pediatric SCD populations. The systematic review by van Veelen et al identified two biofeedback studies and reported favorable findings for selected pain outcomes, including pain frequency or intensity and analgesic use in some settings.5 However, the small evidence base and variation in study design limited confidence in the magnitude and durability of these effects.
Biofeedback was distinguished from ordinary relaxation instruction. Formal biofeedback uses physiological monitoring and structured feedback, whereas breathing exercises and relaxation scripts may be delivered without equipment. In settings where biofeedback equipment or trained personnel were unavailable, simpler coping techniques appeared more feasible, although they could not be considered equivalent interventions.
Implementation in resource-constrained settings would require assessment of equipment costs, staff training, patient acceptability, and the feasibility of integrating sessions into routine care. Larger controlled trials were needed to assess pain intensity and frequency, analgesic consumption, functional outcomes, and the persistence of benefits.
Guided Imagery and Relaxation
Guided imagery encourages patients to direct their attention toward calming or meaningful mental images. Relaxation approaches may include paced breathing, progressive muscle relaxation, and guided audiovisual exercises. These techniques aim to reduce distress and support coping rather than reverse the biological processes responsible for vaso-occlusion.
Dobson and Byrne investigated the use of guided imagery for pain management in young children with SCD.10 Guided imagery and audiovisual relaxation were also considered in the evidence informing the ASH recommendations for acute SCD pain.4 These sources supported the relevance of guided imagery as an intervention warranting further evaluation; however, the evidence was not sufficiently consistent to establish a uniform treatment effect across age groups and clinical settings.
Brief relaxation exercises had practical advantages because they required little equipment and could sometimes be taught by trained healthcare staff. Audio recordings or locally developed scripts could improve access where specialist psychological services were limited. However, feasibility alone did not establish efficacy, and patients could differ in their preferences and ability to engage with imagery or relaxation during severe pain.
These approaches could be offered as optional coping aids during periods of clinical stability and, where appropriate, during acute care. Their use should not delay clinical assessment, analgesia, or escalation of treatment.
Mindfulness-Based Interventions and Hypnosis
Mindfulness-based approaches emphasize nonjudgmental awareness of present-moment experiences, whereas hypnosis uses focused attention and therapeutic suggestion to influence perception and coping.11 Both approaches have been investigated in broader pain populations.
However, the evidence identified in this review did not establish their comparative effectiveness specifically for SCD pain. They were therefore considered research priorities rather than established SCD-specific analgesic interventions. Evidence from other chronic pain populations could inform intervention design, but it could not replace direct evaluation in SCD.
For patients who expressed interest in these approaches, clinicians could discuss them as optional supportive practices while explaining the uncertainty surrounding SCD-specific benefits. Their use should remain compatible with standard treatment and informed patient choice.
Physical and Sensory Interventions
Massage Therapy
Massage involves manual manipulation of soft tissues and may provide relaxation or temporary relief of muscular discomfort. It was investigated among non pharmacological approaches to acute SCD pain and was included in the ASH conditional recommendation for adjunctive treatment.4
The guideline identified small clinical studies, but the overall certainty of evidence for acute pain interventions was very low. Massage appeared potentially acceptable to some patients and relatively accessible where appropriately trained practitioners were available. However, the available evidence did not establish a reliable effect size, duration of benefit, or reduction in subsequent vaso-occlusive episodes.
Massage was therefore best individualized according to patient comfort, preference, and clinical condition. It could not be considered an intervention that reversed vaso-occlusion or prevented SCD complications. Further studies were needed to compare standardized massage protocols with appropriate controls and assess pain intensity, analgesic use, function, adverse events, and patient satisfaction.
Positioning and Comfort Measures
Supportive positioning, comfortable bedding, and adjustments to the care environment may help reduce discomfort associated with immobility or musculoskeletal strain. These measures were generally considered components of supportive nursing care rather than independently validated SCD pain treatments.
Evidence that positioning improved comfort in other clinical settings did not establish an SCD-specific effect on pain intensity, vaso-occlusive processes, or analgesic requirements. Nevertheless, individualized positioning remained appropriate when it improved comfort and did not interfere with clinical assessment, monitoring, or treatment.
Future research could evaluate structured comfort-care protocols alongside usual care, using patient-reported comfort, pain interference, sleep, and analgesic use as outcomes.
Heat and Cold Therapy
Heat and cold have been used for symptom relief in several pain conditions, but their effects in SCD could not be inferred solely from studies of other disorders. The evidence reviewed by ASH did not establish all commonly used thermal interventions as effective treatments for acute SCD pain.4
Claims that heat improved circulation sufficiently to relieve vaso-occlusion, or that cold therapy reliably improved SCD pain, required direct evidence. Thermal measures should be individualized, used in accordance with applicable clinical guidance, and discontinued if uncomfortable. Extreme temperatures and direct applications that could injure the skin should be avoided.
These measures should not replace analgesia, clinical assessment, or evaluation of symptoms that may indicate a complication. Further research was needed to establish whether particular thermal approaches offered meaningful benefits in defined SCD populations.
Transcutaneous Electrical Nerve Stimulation
TENS delivers low-voltage electrical stimulation through electrodes placed on the skin. Although it has been evaluated for several pain conditions, its effectiveness in SCD remained uncertain.
The Cochrane review by Pal et al identified one eligible randomized, double-blind crossover trial involving 22 participants with SCD aged 12–27 years. Across 60 treatment episodes, the trial compared TENS with sham TENS. No clear difference was found in pain ratings at one or four hours or in pain medication use.
A minor itching event was reported during TENS treatment, whereas two participants receiving sham treatment reported worsening pain. The review judged the evidence to be of very low quality because of limitations in trial design, analysis, and reporting.12
Consequently, the available evidence was insufficient to determine whether TENS was beneficial or harmful for SCD pain. Its inclusion in the ASH conditional recommendation for acute pain reflected the broader evidence appraisal and the possibility of adjunctive benefit, rather than proof of established efficacy in SCD.4
TENS was therefore considered an intervention requiring further investigation rather than a routinely established treatment. Future trials should use adequate sample sizes, clearly specified treatment protocols, appropriate sham controls, transparent analyses, and clinically meaningful pain and safety outcomes.
Yoga and Movement-Based Interventions
Yoga combines movement, breathing, and relaxation. It had been investigated in small studies involving acute SCD pain and was included in the ASH conditional recommendation for selected non pharmacological interventions during acute episodes.4 Pediatric systematic reviews also identified a study reporting improvement in selected pain outcomes.5
However, the evidence remained limited, and the effects of yoga could differ according to intervention intensity, patient age, physical function, and whether the intervention was delivered during an acute episode or a period of clinical stability. Participation might not be appropriate during every pain crisis.
Movement-based approaches should be individualized according to the patient’s condition, ability, and preferences. Future studies should evaluate safety, acceptability, appropriate timing, intervention dose, and outcomes such as pain interference, physical function, and quality of life. Evidence from general wellness programs should not be treated as proof of SCD-specific analgesic efficacy.
Virtual Reality and Other Technology-Assisted Interventions
Virtual reality (VR) uses immersive or interactive digital environments to redirect attention and may reduce the subjective experience of pain during some procedures or acute episodes. It was included among the interventions considered in the ASH recommendation for acute SCD pain.4
The pediatric systematic review by van Veelen et al identified a VR study and reported improvement in selected inpatient pain outcomes.5 However, the evidence was based on a small number of studies and did not establish that VR reduced the frequency of future vaso-occlusive episodes, prevented hospitalization, or provided sustained relief of chronic pain.
VR appeared potentially attractive for some pediatric patients, but implementation required access to suitable devices, cleaning and maintenance procedures, staff support, and attention to individual tolerance. Costs, electricity supply, device availability, and technical support could limit its use in resource-constrained settings.
Technology-assisted interventions therefore required assessment of both clinical effectiveness and implementation feasibility. Their benefits could not be generalized to unrelated digital tools or applications without intervention-specific evidence.
Acupuncture and Other Provider-Delivered Integrative Approaches
Acupuncture has been investigated for several pain conditions and was discussed in the ASH guideline in the context of provider-delivered integrative approaches for chronic SCD pain in adults. The guideline conditionally suggested approaches such as massage and acupuncture when available and tolerated, based on very-low-certainty evidence and individual patient preference.4
This recommendation did not establish that acupuncture had a well-established analgesic effect in SCD. The guideline identified limitations in the evidence base, particularly for children, and emphasized the importance of cost, access, practitioner training, and patient burden.
In clinical practice, acupuncture could be discussed as an optional adjunct where appropriate services were available and patients wished to consider it. It should be delivered within a comprehensive pain-management plan and should not replace indicated pharmacological treatment. Further SCD-specific controlled trials were needed to establish efficacy, safety, acceptability, and cost-effectiveness.
Spiritual, Religious, and Social Coping
Prayer, religious participation, spiritual reflection, family support, and peer support may be important coping resources for some individuals living with SCD. These practices can provide meaning, emotional support, social connection, and a sense of continuity during illness.
However, the importance of spiritual coping to an individual did not establish that a spiritual intervention directly reduced vaso-occlusion or the physiological processes underlying SCD pain. Evidence from general populations concerning spirituality and well-being could not be treated as direct evidence of analgesic efficacy in SCD.
Healthcare professionals could respectfully ask whether spiritual or religious practices were important to a patient’s care and facilitate access to desired support. Participation should remain voluntary, culturally sensitive, and inclusive of people with different beliefs or no religious affiliation. Spiritual care should complement, rather than replace, clinical pain management.
Social support was similarly relevant to the experience of living with a chronic condition, but its effect on specific SCD pain outcomes required direct investigation. Future research could examine whether structured peer-support or family-based interventions improved coping, treatment engagement, emotional well-being, and pain-related function.
Summary of Selected Clinical Evidence
Table 1 summarizes representative primary studies, systematic reviews, and guidelines that informed this review. It distinguishes direct SCD-specific evidence from evidence syntheses and highlights the principal limitations affecting interpretation. The table does not represent an exhaustive inventory of all studies potentially eligible for inclusion.
Table 1Selected Evidence on Non Pharmacological Pain Management in Sickle Cell DiseaseStudyDesign and PopulationIntervention or FocusMain Findings and LimitationsGil et al, 1996.7Randomized study involving 64 African American adults with SCDCognitive coping skills training versus disease educationThe three-session intervention increased coping attempts, reduced negative thinking, and lowered reported pain responses to laboratory stimuli. The findings did not establish reductions in naturally occurring pain crises or healthcare utilization.Anie et al, 2002.8Clinical study involving people with SCDSelf-help, manual-assisted CBTThe study examined a structured behavioral pain-management approach. Its findings required interpretation in relation to the study design, population, and outcomes measured.Dobson and Byrne, 2014.10Original research involving young children with SCDGuided imageryThe study examined guided imagery for pain management in young children.
Its findings were specific to the intervention and population studied and could not automatically be generalized to other age groups or clinical outcomes.Brandow et al, 2020.4Evidence-based clinical guidelineMassage, yoga, TENS, virtual reality, guided audiovisual relaxation, and integrative approachesThe guideline conditionally recommended selected adjunctive interventions for acute pain and certain provider-delivered integrative approaches for chronic pain. The recommendations were based on very-low-certainty evidence and emphasized implementation constraints.Pal et al, 2020.12Cochrane systematic review; one eligible crossover randomized controlled trial involving 22 participants aged 12–27 yearsTENS versus sham TENSThe review found no clear difference in pain ratings or analgesic use. The evidence was of very low certainty, and benefit or harm could not be established confidently.Van Veelen et al, 2023.5Systematic review of 10 articles involving 422 participantsCBT, biofeedback, massage, virtual reality, and yogaThe review reported favorable findings for selected interventions and outcomes.
Heterogeneity prevented quantitative pooling and limited firm conclusions.Garrett et al, 2023.6Scoping review of pediatric vaso-occlusive painMultiple nonpharmacological interventionsThe review mapped the evidence on interventions for acute pediatric pain and highlighted limitations in the available literature. Its findings did not establish equivalent efficacy across interventions.Palermo et al, 2024.13Multicenter randomized controlled trial; 111 adolescents included in the randomized analysisDigital CBT versus education controlDigital CBT improved average pain intensity and reduced pain days at six months. The findings supported this specific intervention in adolescents but did not establish effectiveness across all age groups or for acute inpatient pain.Notes: The evidence summarized in Table 1 illustrated the importance of intervention-specific interpretation.
The digital CBT trial provided a comparatively strong controlled evaluation of a defined intervention in a specific population. In contrast, the Cochrane review of TENS identified.Abbreviations: CBT, cognitive behavioral therapy; RCT, randomized controlled trial; SCD, sickle cell disease; TENS, transcutaneous electrical nerve stimulation; VR, virtual reality.
Implications for Clinical Practice and Low- and Middle-Income Countries
Non pharmacological pain management was particularly relevant in low- and middle-income countries (LMICs), where many people living with sickle cell disease (SCD) faced limited access to specialist pain services, psychological therapies, and comprehensive multidisciplinary care. However, the feasibility of delivering an intervention did not necessarily establish its clinical effectiveness.
Brief relaxation exercises, guided breathing, and selected self-management resources generally required relatively little equipment. Structured cognitive behavioral therapy (CBT), however, required appropriate training and supervision, although digital delivery and supported task-sharing models offered potential opportunities to expand access. Biofeedback, transcutaneous electrical nerve stimulation (TENS), and virtual reality (VR) required varying degrees of equipment, maintenance, staff training, and reliable infrastructure.
Several barriers to implementation were identified, including limited healthcare funding, shortages of trained personnel, competing clinical priorities, out-of-pocket costs, unreliable internet connectivity, language differences, and limited access to private consultation spaces. Cultural beliefs about pain, family involvement, religious practices, and expectations regarding treatment could also influence the acceptability of these interventions. These factors required context-specific assessment rather than assumptions about their uniformity across African settings.
In Uganda and other sub-Saharan African countries, implementation research was needed to assess patient preferences, existing pain-management pathways, staff capacity, device availability, and the costs associated with delivering interventions. Intervention materials required adaptation to local languages and cultural contexts, with patient involvement in their design. Task-sharing approaches were potentially useful in settings with shortages of specialist professionals; however, their safety, effectiveness, training requirements, and supervision arrangements required systematic evaluation.
Digital interventions offered potential opportunities to reduce travel and scheduling burdens but could exclude patients without compatible devices, reliable internet connectivity, sufficient data, or adequate digital literacy. Offline materials, audio resources, and supported face-to-face approaches were therefore potentially more appropriate in some settings. Comparative research was needed to establish the feasibility and effectiveness of these alternative delivery models.
Importantly, non pharmacological approaches were not intended to replace timely analgesia, appropriate assessment of acute pain, or evidence-based disease-modifying treatment. In settings where access to essential medicines was limited, introducing self-management interventions risked shifting responsibility for inadequate pain relief onto patients. Implementation strategies therefore needed to strengthen comprehensive SCD care and expand patient choice rather than normalize avoidable gaps in treatment.
Research Gaps and Priorities
Several important evidence gaps were identified. First, the available evidence base contained relatively few adequately powered randomized controlled trials. Many studies involved small samples, short follow-up periods, and inconsistent outcome measures, which limited comparisons across interventions.
Future research was therefore needed to incorporate validated measures of pain intensity and frequency, functional interference, quality of life, analgesic consumption, adverse events, and healthcare utilization.
Second, the strength of evidence varied substantially by intervention. A multicenter randomized controlled trial demonstrated benefits of digital CBT for selected pain outcomes among adolescents with SCD, whereas the available evidence for TENS remained insufficient to establish benefit or harm.9,13 Comparable intervention-specific evaluations were needed for massage, guided imagery, biofeedback, mindfulness-based approaches, and other commonly used strategies.
Third, the reviewed literature highlighted the need to distinguish acute vaso-occlusive pain from chronic pain and to investigate whether intervention effects varied across age groups, disease severity, healthcare settings, and patterns of pain. Further studies were also needed to assess treatment adherence, intervention acceptability, and the durability of reported benefits.
Fourth, a substantial need for implementation research was identified in African settings. Such research needed to assess feasibility, affordability, workforce requirements, cultural acceptability, and integration into existing clinical services. Community-based and task-shared approaches were considered potentially relevant, particularly where specialist services were limited; however, their safety and effectiveness required empirical evaluation rather than assumption.
Finally, future studies needed to compare interventions with appropriate control conditions, report adverse events and participant attrition transparently, and determine whether combinations of behavioral and physical approaches provided additional benefits beyond usual care.
Conclusion
Non pharmacological interventions were identified as potentially valuable adjuncts to comprehensive pain management in SCD, although the strength of evidence varied across approaches. The most directly relevant evidence included studies of CBT and selected interventions such as biofeedback, massage, guided relaxation, yoga, and VR. Nevertheless, limitations in sample sizes, study designs, and outcome measurement restricted the certainty of conclusions regarding their effectiveness.
Digital CBT demonstrated improvements in selected pain outcomes among adolescents with SCD, whereas the available evidence for TENS remained insufficient to establish benefit or harm.9,13 Other approaches, including mindfulness, hypnosis, acupuncture, and spiritual interventions, required careful differentiation between indirect evidence from other populations and demonstrated SCD-specific effectiveness.
The findings indicated that clinical decisions needed to be individualized according to patient preferences, intervention-specific evidence, feasibility, and available resources. Non pharmacological approaches were intended to complement, rather than replace, timely pharmacological treatment and comprehensive clinical care. Further well-designed clinical trials and implementation studies, particularly in sub-Saharan Africa, were needed to establish which interventions were effective, acceptable, affordable, and sustainable across different SCD populations and healthcare settings.