Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice
© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| Errataetall: |
CommentIn: J Bone Miner Res. 2023 Nov;38(11):1547-1548. - PMID 37975545 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
|---|---|
| Enthalten in: |
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research - 38(2023), 11 vom: 04. Nov., Seite 1560-1576 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Khajuria, Deepak Kumar [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.12.2023 Date Revised 11.04.2024 published: Print-Electronic CommentIn: J Bone Miner Res. 2023 Nov;38(11):1547-1548. - PMID 37975545 Citation Status MEDLINE |
|---|
| doi: |
10.1002/jbmr.4902 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360959288 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360959288 | ||
| 003 | DE-627 | ||
| 005 | 20240411232105.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/jbmr.4902 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1372.xml |
| 035 | |a (DE-627)NLM360959288 | ||
| 035 | |a (NLM)37597163 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Khajuria, Deepak Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.12.2023 | ||
| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Bone Miner Res. 2023 Nov;38(11):1547-1548. - PMID 37975545 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). | ||
| 520 | |a Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a ANALGESIC | |
| 650 | 4 | |a BONE REGENERATION | |
| 650 | 4 | |a CANNABIDIOL | |
| 650 | 4 | |a CANNABIGEROL | |
| 650 | 4 | |a FRACTURE HEALING | |
| 650 | 7 | |a cannabigerol |2 NLM | |
| 650 | 7 | |a J1K406072N |2 NLM | |
| 650 | 7 | |a Cannabidiol |2 NLM | |
| 650 | 7 | |a 19GBJ60SN5 |2 NLM | |
| 650 | 7 | |a Cannabinoids |2 NLM | |
| 650 | 7 | |a Anti-Inflammatory Agents, Non-Steroidal |2 NLM | |
| 650 | 7 | |a Minerals |2 NLM | |
| 700 | 1 | |a Karuppagounder, Vengadeshprabhu |e verfasserin |4 aut | |
| 700 | 1 | |a Nowak, Irena |e verfasserin |4 aut | |
| 700 | 1 | |a Sepulveda, Diana E |e verfasserin |4 aut | |
| 700 | 1 | |a Lewis, Gregory S |e verfasserin |4 aut | |
| 700 | 1 | |a Norbury, Christopher C |e verfasserin |4 aut | |
| 700 | 1 | |a Raup-Konsavage, Wesley M |e verfasserin |4 aut | |
| 700 | 1 | |a Vrana, Kent E |e verfasserin |4 aut | |
| 700 | 1 | |a Kamal, Fadia |e verfasserin |4 aut | |
| 700 | 1 | |a Elbarbary, Reyad A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research |d 1991 |g 38(2023), 11 vom: 04. Nov., Seite 1560-1576 |w (DE-627)NLM012611115 |x 1523-4681 |7 nnns |
| 773 | 1 | 8 | |g volume:38 |g year:2023 |g number:11 |g day:04 |g month:11 |g pages:1560-1576 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/jbmr.4902 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 38 |j 2023 |e 11 |b 04 |c 11 |h 1560-1576 | ||