Evidence map›Paper›PMID 40821360›Full record

ReviewJOR spine2025

A Conceptual Review of Naturally Occurring Toxins and Venoms as Peptide Blockers to Combat Chronic Low Back Pain.

James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu

Abstract readReview
In one paragraph

Review in JOR spine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

James MelroseRaymond Purves Bone and Joint Research Laboratory Kolling Institute, Sydney University Faculty of Medicine and Health, Northern Sydney Area Health District, Royal North Shore Hospital St. Leonards New South Wales Australia.ORCID https://orcid.org/0000-0001-9237-0524
Stone SimaSpine Labs, Department of Orthopaedic Surgery, St. George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales Kogarah, Sydney New South Wales Australia.ORCID https://orcid.org/0000-0002-1675-1496
Neha ChopraSpine Labs, Department of Orthopaedic Surgery, St. George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales Kogarah, Sydney New South Wales Australia.
Ashish DiwanSpine Labs, Department of Orthopaedic Surgery, St. George & Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales Kogarah, Sydney New South Wales Australia.ORCID https://orcid.org/0000-0003-1037-8421
Zi GuNanoBiotechnology Research Laboratory, School of Chemical Engineering University of New South Wales Kensington, Sydney New South Wales Australia.ORCID https://orcid.org/0000-0002-7153-6596

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers. Methods: This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures. Results: Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca Conclusion: Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.

Indexed as

blocking of voltage gated Ca2+ channelsconotoxinsdorsal root ganglionintervertebral disc degenerationlow back painnerve‐blocksneuroinflammationnigriventer venom peptidesnociception

Identifiers

PMID40821360
PMCPMC12355398

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.