Three key insights from NeuPSIG 2025 that are reshaping chronic pain research

Approximately 700 researchers, clinicians, and industry leaders convened in Berlin from 4th - 6th September for NeuPSIG 2025, creating an atmosphere of focused intensity and collaboration. Despite its modest size, the meeting brought together a tightly knit and highly specialized community, united by a shared commitment to advancing neuropathic pain science. The conference served as a high-impact platform for unveiling novel insights-from mechanistic discoveries to innovations in clinical trial design-highlighting the rapidly evolving landscape of pain neuroscience.

Here are five key developments from the meeting that captured the attention of Dr. Marco Calabresi, senior medical director for neuroscience at Fortrea, and his thoughts on what may shape the strategic direction of your next neuroscience or pain-focused clinical trial.

1. New Global Guideline Reshapes Neuropathic Pain Treatment Landscape

A landmark update from the Neuropathic Pain Special Interest Group (NeuPSIG), published in The Lancet Neurology in May 20251, delivers a comprehensive overhaul of treatment recommendations for neuropathic pain, integrating both pharmacotherapy and non-invasive neuromodulation strategies. This systematic review and meta-analysis spans 313 randomized controlled trials and over 48,000 adult participants, making it the most extensive evidence synthesis in this domain to date.

Key Takeaways for Clinicians and Innovators

• First-line therapies now include tricyclic antidepressants (TCAs), Serotonin-norepinephrine reuptake inhibitors (SNRIs), and α2δ-ligands, based on moderate certainty of evidence and favorable benefit-risk profiles¹.
• Second-line options feature topical agents like capsaicin 8% patches, capsaicin cream, and lidocaine 5% plasters, recommended especially for localized peripheral neuropathic pain¹.
• Third-line treatments include botulinum toxin type A, repetitive transcranial magnetic stimulation (rTMS), and opioids, with cautious use advised due to safety concerns and limited evidence¹.

Implications for Clinical Trials and Drug Development:

This guideline sets a new benchmark for trial design and therapeutic evaluation:

• Higher standards for evidence: Future trials must address the modest efficacy and high heterogeneity observed across existing studies. Large, placebo- or sham-controlled trials with longer follow-up durations are now essential¹.
• Phenotype-driven stratification: The guideline highlights the need for sensory phenotype-based trial designs, which could unlock more targeted and effective therapies¹.
• Combination therapies: Despite their clinical relevance, current evidence is insufficient to support specific drug combinations¹. This opens a strategic opportunity for sponsors to explore novel multimodal regimens.
• Neuromodulation innovation: With rTMS now included, albeit as a third-line option, the door is open for next-generation non-invasive neuromodulation devices to demonstrate superiority in well-powered trials¹.

2. Precision Phenotyping for Neuropathic Pain Subtypes2

Quantitative sensory testing (QST), skin biopsies, genetic profiling of the electrogenisome, and biomarker integration are driving a more refined classification of neuropathic pain phenotypes. This evolution supports targeted trial designs and enrichment strategies that may enhance signal detection and mitigate placebo response-particularly critical in heterogeneous populations such as diabetic peripheral neuropathy and postherpetic neuralgia².

While encouraging, the scalability and operational feasibility of phenotyping approaches in confirmatory trials remain limited. Standardization across sites, cost implications, and regulatory acceptance are ongoing challenges².

In contrast, exploratory phase trials stand to benefit significantly from phenotypic enrichment, especially when stratifying patients by gain-of-function (e.g., irritable nociceptor) versus loss-of-function (non-irritable nociceptor) profiles. This stratification may improve responder identification and inform mechanism-specific therapeutic development².

As the field matures, integrating phenotyping into adaptive trial designs and biomarker-led stratification frameworks could bridge the gap between mechanistic insight and clinical utility.

VER-01: hope for chronic low back pain sufferers

At NeuPSIG 2025, a new chapter in cannabinoid-based therapeutics was unveiled with the presentation of VER-CLBP-001, the first phase 3 trial evaluating VER-01 for chronic low back pain^3,4.

VER-01 contains a patented cannabinoid-based active ingredient derived from plant genetics, including THC, cannabigerol and cannabidiol. VER-01 is administered orally and the optimal dose is titrated on a patient-by-patient basis.

Designed for individualized dosing, it is being developed to address the complex landscape of chronic pain, including osteoarthritis and painful diabetic neuropathy.

A Thoughtful Trial Design

The study featured a four-phase structure^3,4:

• Phase A: Patients were titrated and randomized to VER-01 or placebo for 12 weeks.
• Phase B: All participants received open-label VER-01 for 6 months.
• Phases C & D: Focused on long-term safety and sustained efficacy.

What Did the Data Show?

By the end of Phase A, VER-01 demonstrated a statistically significant 0.6-point reduction in pain scores. But the real story lies in the subgroups: patients with severe pain, neuropathic features, and long-standing CLBP experienced notable improvements^3,4.

Beyond pain relief, participants reported better sleep, physical function, and quality of life-benefits that were maintained throughout the extended treatment period in Phase B^3,4.

VER-01 was well tolerated, with side effects mostly mild to moderate and concentrated during the titration phase. Importantly, there were no signs of dependence or abuse potential, a critical consideration in cannabinoid research^3,4.

The full dataset is expected in an upcoming publication, but early signals suggest VER-01 could be a meaningful addition to the chronic pain toolbox-especially for patients underserved by conventional therapies.

What This Means for Your Next Pain Trial

The chronic pain research landscape is evolving-faster and more decisively than many anticipated. For clinical research directors and medical leads, this shift brings both strategic opportunity and operational complexity. Success now hinges on targeted patient selection, precision dosing strategies, and trial designs that reflect the multifactorial nature of pain-especially when exploring novel mechanisms like cannabinoid-based interventions.

The momentum from NeuPSIG 2025 is not just about isolated breakthroughs. It signals a maturing field, where diverse approaches-from sensory phenotyping to biomarker-driven stratification-are beginning to converge and deliver meaningful results. In this environment, thoughtful trial execution is what separates programs that move forward from those that stall.

If you are planning your next neuroscience or pain-focused trial, now is the time to integrate these insights. Let's explore how Fortrea can help you navigate this dynamic space-from protocol design to global execution-with scientific rigor and operational excellence.

Ready to turn these insights into your next successful neuroscience trial? Let's talk about how Fortrea can help you navigate this evolving landscape.

• 1. Soliman N, Moisset X, et al; NeuPSIG Review Update Study Group. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. Lancet Neurol. 2025 May;24(5):413-428. doi: 10.1016/S1474-4422(25)00068-7. PMID: 40252663.
• 2. Calvo et al: From evidence to practice: international guidelines for neuropathic pain treatment, local adaptations and insights. NeuPSIG 2025 Workshop. https://neupsigcongress.org/scientific-programme/program-overview/. Last accessed 11th September 2025.
• 3. Argoff, C: Pivotal Phase 3 data on the efficacy and safety of VER-01 in chronic low back pain. Industry Lunchtime Symposium. NeuPSIG 2025. https://neupsigcongress.org/exhibitors-and-supporters/industry-sponsored-sessions/. Last accessed 11th September 2025.
• 4. Efficacy and Safety of VER-01 in the Treatment of Patients With Chronic Non-specific Low Back Pain. https://clinicaltrials.gov/study/NCT04940741?intr=VER-01&limit=25&page=1&rank=3. Updated 4th August 2024. Accessed 16th September 2025.