Rewiring the Brain-Immune Axis for Chronic Pain Using Transcranial Magnetic Stimulation in Psoriatic Arthritis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in STAT3 phosphorylation in circulating monocytes
研究概览
简要总结
Despite advances in immunomodulatory therapies, many Psoriatic arthritis (PsA) patients experience persistent pain unrelated to clinical active joint inflammation. Recent evidence suggests the Inferior Parietal Lobule (IPL) serves as a neuroimmune hub linking central neural activity with peripheral immune dysregulation. In a prior feasibility study, a single L-IPL-targeted TMS session reduced pain and altered immune signalling in inflammatory arthritis by reducing STAT3 phosphorylation in circulating monocytes. This study builds on those findings by evaluating whether rTMS over 4 weeks can induce sustained immune reprogramming while providing meaningful pain relief.
详细描述
Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease (IMID) characterised by musculoskeletal pain, enthesitis, and synovitis. While advances in immunomodulatory therapies have improved control of inflammation, approximately one-third of people with PsA continue to report persistent pain despite achieving low disease activity by clinical criteria. This dissociation between detectable inflammation and ongoing pain suggests a role for central nervous system (CNS) mechanisms in the persistence of symptoms. Emerging evidence from neuroimaging studies has highlighted the inferior parietal lobule (IPL) as a brain region implicated in both pain perception and immune signalling. Prior work in inflammatory arthritis shows that IPL grey-matter volume and functional connectivity correlate with peripheral inflammation and pain.
These findings suggest that the IPL may act as a neuroimmune hub, integrating nociceptive input and modulating pain perception and immune function via top-down signalling pathways. Recent translational research across cancer, cardiovascular, and IMIDs has established that brain activity can shape peripheral immune responses, and thereby influence disease progression.
In PsA, chronic pain may therefore reflect not only residual joint pathology but also maladaptive brain immune interactions that perpetuate inflammation and amplify pain processing. This under-explored pathophysiological loop constitutes a critical unmet therapeutic target in PsA and other IMIDs.
Psoriatic arthritis-related pain is only partially explained by joint specific inflammation. Despite excellent control of peripheral inflammation by contemporary immune modulatory regimes, as many as 30% of patients continue to report disabling levels of pain, thus comprising an urgent unmet clinical need.
Our group has been among the first to evidence a contributory role of the CNS as an explanation for this debilitating symptom. Neuroimaging studies in inflammatory arthritis have highlighted the inferior parietal lobule (IPL) as a potential neuroimmune hub: altered IPL grey-matter volume and functional connectivity have been linked to both systemic inflammation and pain, suggesting this region may integrate nociceptive and immune signals. These findings are consistent with broader evidence implicating IPL hyperconnectivity in pro-nociceptive brain networks observed in chronic pain conditions such as fibromyalgia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participants are masked to group allocation. The rTMS operator is not masked due to the need to position the coil at different stimulation sites.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥ 18 years ≤ 75 years
- •Diagnosis of PsA according to CASPAR (Classification Criteria for Psoriatic Arthritis).
- •Low disease activity (no more than one joint with clinically active swelling) or remission
- •Chronic pain for at least 3 months and VAS (Visual Analogue Scale) pain ≥30 mm
- •Stable treatment ≥3 months prior to entering the study
- •Able and willing to maintain medication for the duration study
- •Able to undergo MRI and TMS procedures
排除标准
- •Inability to provide written informed consent.
- •Severe physical impairment (e.g. blindness, deafness, paraplegia) Pregnant, planning pregnancy or breast feeding.
- •Severe claustrophobia precluding MRI.
- •Contraindications to MRI (e.g. metal implants/ pacemaker).
- •Contraindications to TMS (e.g. history of seizures).
- •Serious infection including sepsis, tuberculosis and opportunistic infections such as invasive fungal infections.
- •Major confounding neurological disease including Multiple
- •Sclerosis, Stroke, Traumatic Brain Injury, Parkinson's Disease, Alzheimer's Disease
研究组 & 干预措施
rTMS (Left Inferior Parietal Lobule)
Participants receive active repetitive transcranial magnetic stimulation (rTMS) targeted to the left inferior parietal lobule (L-IPL). Stimulation is delivered at 10 Hz, 90% resting motor threshold, 1200 pulses per session, across 12 sessions over 4 weeks. This arm is designed to evaluate whether neuromodulation of the L-IPL alters immune signalling and reduces persistent pain in psoriatic arthritis.
干预措施: Active Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
rTMS (Vertex Stimulation)
Participants receive control rTMS delivered to the cranial vertex, a site not expected to modulate neuroimmune pathways relevant to pain. Stimulation parameters match the active arm (10 Hz, 90% resting motor threshold, 1200 pulses per session, 12 sessions over 4 weeks). This arm controls for nonspecific effects of rTMS, including sensory experience and participant expectations.
干预措施: Control Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
结局指标
主要结局
Change in STAT3 phosphorylation in circulating monocytes
时间窗: Week 1 to Week 4
Assessment of the effect of left-inferior parietal lobule (L-IPL) targeted repetitive transcranial magnetic stimulation (rTMS) on immune systems; specifically changes in circulating monocytes intracellular signalling, primarily STAT3 phosphorylation levels, assessed via flow cytometry, before and after rTMS targeting L-IPL compared with the control (vertex stimulation) condition.
次要结局
- Changes in genetic expression of circulating immune cells, monocytes and CD8+ T-cells, using transcriptomic assays (RNA-seq).(Week 1 to Week 4)
- Changes in trained immunity set-points in monocytes and CD8+ T-cells, by investigating their epigenetic profile changes using Cleavage Under Targets and Tagmentation (CUT&TAG assay).(Week 1 to Week 4)
- Changes in pain severity as measured by the Pain Number Rating Scale.(Week 1 to Week 4)
- Changes in pain severity as measured by Widespread Pain as part of the American College of Rheumatology Fibromyalgia scale.(Week 1 to Week 4)
- Changes in putative pain confounders as measured by PROMIS-Fatigue.(Week 1 to Week 4)
- Changes in putative pain confounders as measured by PROMIS-Depression.(Week 1 to Week 4)
- Changes in putative pain confounders as measured by PROMIS-Sleep Related Impairment.(Week 1 to Week 4)
- Changes in putative pain confounders as measured by PROMIS-Physical functioning short form.(Week 1 to Week 4)
- Changes in putative pain confounders as measured by PROMIS-Pain Interference.(Week 1 to Week 4)
- Changes in PsA disease activity as measured by Disease Activity in Psoriatic Arthritis (DAPSA).(Week 0 to Week 4)
- Changes in PsA disease activity as measured by Minimal Disease Activity (MDA).(Week 0 to Week 4)
- Changes in PsA disease activity as measured by Body Surface Area (BSA).(Week 0 to Week 4)
- Changes in blood protein levels of inflammatory cytokines/chemokines.(Week 1 to Week 4)