Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model

Goto, Taichi; Sapio, Matthew R.; Maric, Dragan; Robinson, Jeffrey M.; Domenichiello, Anthony F.; Saligan, Leorey N.; Mannes, Andrew J.; Iadarola, Michael J.

doi:10.1096/fj.202100347r

Cited by 8 publications

(7 citation statements)

References 99 publications

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“…Following surgery, the rat remained on an insulated heating pad until full recovery from anesthesia before being moved back to its cage and observed periodically until full ambulatory recovery. All wounds stopped bleeding within ∼5 minutes and appeared outwardly to have largely healed within 5-6 days, similar to what has been described for unilateral plantar incision 15, 31 . Simple schematic diagrams are included in each results figure to show the type of incision injury used.…”

Section: Methodssupporting

confidence: 81%

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Bavencoffe,

Lopez,

Johnson

et al. 2024

Preprint

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Nociceptors with somata in dorsal root ganglia (DRGs) exhibit an unusual readiness to switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Ongoing activity (OA) during this state is present in vivo in rats months after spinal cord injury (SCI), and has been causally linked to SCI pain. OA induced by various neuropathic conditions in rats, mice, and humans is retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. An important question is whether similar nociceptor OA is induced by painful conditions other than neuropathy. The present study shows that probable nociceptors dissociated from DRGs of rats subjected to postsurgical pain (induced by plantar incision) exhibit OA. The OA was most apparent when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This latent hyperactivity persisted for at least 3 weeks, whereas behavioral indicators of affective pain (hindpaw guarding and increased avoidance of a noxious substrate in an operant conflict test) persisted for 1 week or less. An unexpected discovery was latent OA in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to amplify hyperalgesic priming and to drive anxiety-related hypervigilance.

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Section: Methodssupporting

confidence: 81%

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Bavencoffe,

Lopez,

Johnson

et al. 2024

Preprint

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“… 26 , 27 Enhanced Nppb mRNA expression has been observed in the epidermis at the wound edge of surgical incisions. 27 BNP regulates angiogenesis via guanylyl cyclase‐A in ischemic muscles and the heart. 28 Therefore, Nppb mRNA expression may be associated with disrupted re‐epithelialisation and angiogenesis in wound infection.…”

Section: Discussionmentioning

confidence: 99%

“…NPPB is cleaved into brain natriuretic peptide (BNP), which acts as a cardiac hormone. There are few reports on BNP and NPPB protein expression in wounds 26,27 . Enhanced Nppb mRNA expression has been observed in the epidermis at the wound edge of surgical incisions 27 .…”

Section: Discussionmentioning

confidence: 99%

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Expression levels of NPPB, ITGB6, CPNE4, EML5, and ITSN1 in fresh exudates swabbed from critically colonised and infected full‐thickness wounds in rats

Takizawa

Minematsu

Nakagami

et al. 2022

International Wound Journal

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Pressure injury management requires reliable identification of critical colonisation due to lack of infection signs. Our research group previously proposed the mRNAs natriuretic peptide B ( Nppb ), integrin subunit beta 6 ( Itgb6 ), copine 4 ( Cpne4 ), echinoderm microtubule ‐ associated protein like 5 , and intersectin 1 as candidate markers in pooled exudates of critically colonised wounds. However, it is unclear whether mRNAs or proteins of the candidate genes would be suitable as biomarkers in fresh exudate. Therefore, this study aimed to evaluate the validity of the mRNAs and proteins as fresh exudate markers for critical colonisation. Three wound models of normal healing, critical colonisation, and infection were created in rats. Fresh swab‐collected exudates were collected, and mRNA and protein expression levels were measured. In the fresh wound exudates, the detection frequency of Itgb6 tended to decrease in the critically colonised and infected wounds ( P = .067), and those of Cpne4 and Nppb tended to be lower in the infected wounds than in the normal healing and critically colonised wounds ( P = .006 and .067, respectively). In contrast, there was no difference in protein expression in the exudates. This study suggests that Itgb6 mRNA in fresh exudates is a promising biomarker for critical colonisation.

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“…MMPs hydrolyze ECM components to influence their dynamic balance of degradation and restructuring, participate in a variety of cell physiological and pathological process, and influence wound healing and reconstruction. MMP23 is a unique component of the MMP protein family with characteristic domains and functions, degrading ECM proteins, cleaving cell–surface receptors, releasing apoptotic ligands, and activating chemokines and cytokines. − …”

Section: Introductionmentioning

confidence: 99%

Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan

Xia

Yang

et al. 2023

ACS Appl. Bio Mater.

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Skin wounds may cause severe financial and social burden due to the difficulties in wound healing. Original inert dressings cannot meet multiple needs in the process of wound healing. Therefore, the development of materials to accelerate healing progress is essential and urgent. In the previous study, we found that the homogeneously synthesized hydroxybutyl chitosan (HBCS) had an effective performance in promoting wound healing. Proteomic analysis of the same specimen suggested that matrix metalloproteinase 23 (MMP23) may play a key role in HBCS expediting the progress of wound healing. In this work, we aim to reveal the underlying mechanism of MMP23 in the dynamic process of cutaneous proliferation and repair period. In order to regulate the expression level of MMP23 in the local wound area, we leaded in adeno-associated virus (AAV) to specifically decreased expression quantity of MMP23 in rat skin. In contrast to the negative control groups, we found that the wound closed faster and the collagen fibers and neovascularization were significantly increased in AAV groups. These findings highlighted that MMP23 was involved in wound healing after traumatic injury, and managing the expression of MMP23 could be a potential intervention target to accelerate wound healing.

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Longitudinal peripheral tissue RNA‐Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 99 publications

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Widespread latent hyperactivity of nociceptors outlasts enhanced avoidance behavior following incision injury

Expression levels of NPPB, ITGB6, CPNE4, EML5, and ITSN1 in fresh exudates swabbed from critically colonised and infected full‐thickness wounds in rats

Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan

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