ArticleBiochemical pharmacology2009
Morphine-induced early delays in wound closure: involvement of sensory neuropeptides and modification of neurokinin receptor expression.
Article in Biochemical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.International journal of oral science · 2025Guideline
- Topical application of morphine for wound healing and analgesia in patients with oral lichen planus: a randomized, double-blind, placebo-controlled study.Clinical oral investigations · 2018Trial
- Low dose naloxone mitigates opioid tolerance and dependence and restores mesenchymal stem cell function for cell therapy in addiction.Scientific reports · 2025Article
- Innervated Biomaterials for Improved Cutaneous Wound Healing: A Review of Recent Advancements and Future Prospects.International journal of nanomedicine · 2025Review
- Review
- The anti-nociceptive effect of BPC-157 on the incisional pain model in rats.Journal of dental anesthesia and pain medicine · 2022Article
- Future roles of artificial intelligence in early pain management of newborns.Paediatric & neonatal pain · 2021Review
- The Altered Migration and Distribution of Systemically Administered Mesenchymal Stem Cells in Morphine-Treated Recipients.Stem cell reviews and reports · 2021Article
- Tissue Regeneration: The Dark Side of Opioids.International journal of molecular sciences · 2021Review
- Keratin Scaffolds Containing Casomorphin Stimulate Macrophage Infiltration and Accelerate Full-Thickness Cutaneous Wound Healing in Diabetic Mice.Molecules (Basel, Switzerland) · 2021Article
- Primary Ciliary Signaling in the Skin-Contribution to Wound Healing and Scarring.Frontiers in cell and developmental biology · 2020Review
- Investigation of the effects of systemic meperidine administration on fascia healing in an experimental rat model.Acta cirurgica brasileira · 2020Article
- Bidirectional Regulation of Opioid and Chemokine Function.Frontiers in immunology · 2020Review
- Article
- The Impact of Morphine on the Characteristics and Function Properties of Human Mesenchymal Stem Cells.Stem cell reviews and reports · 2018Article
- Opioids prevent regeneration in adult mammals through inhibition of ROS production.Scientific reports · 2018Article
- Severe pain during wound care procedures: A cross-sectional study protocol.Journal of advanced nursing · 2018Article
- Local Resiniferatoxin Induces Long-Lasting Analgesia in a Rat Model of Full Thickness Thermal Injury.Pain medicine (Malden, Mass.) · 2017Article
- Relationship between opioid treatment and rate of healing in chronic wounds.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2017Observational
- Burn wound healing and treatment: review and advancements.Critical care (London, England) · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Dose-limiting side effects of centrally acting opioid drugs have led to the use of topical opioids to reduce the pain associated with chronic cutaneous wounds. However, previous studies indicate that topical morphine application impairs wound healing. This study was designed to elucidate the mechanisms by which morphine delays wound closure. Rats were depleted of sensory neuropeptides by treatment with capsaicin, and full-thickness 4-mm diameter wounds were excised from the intrascapular region. Wounds were treated topically twice daily with 5mM morphine sulfate, 1mM substance P, 1mM neurokinin A, or 5mM morphine combined with 1mM substance P or neurokinin A and wound areas assessed. During closure, wound tissue was taken 1, 3, 5, and 8 days post-wounding from control and morphine-treated rats and immunostained for neurokinin receptors and markers for macrophages, myofibroblasts, and vasculature. Results obtained from capsaicin-treated animals demonstrated a significant delay in the early stages of wound contraction that was reversed by neuropeptide application. Treatment of capsaicin-treated rats with topical morphine did not further delay wound closure, suggesting that topical opioids impair wound closure via the inhibition of peripheral neuropeptide release into the healing wound. Morphine application altered neurokinin-1 and neurokinin-2 receptor expression in inflammatory and parenchymal cells essential for wound healing in a cell-specific manner, demonstrating a direct effect of morphine on neurokinin receptor regulation within an array of cells involved in wound healing. These data provide evidence indicating a potentially detrimental effect of topical morphine application on the dynamic wound healing process.
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Registered trials
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.