The Effect of Lactate on Pain, Oxygenation, and Wound Healing
H Haller, M Rapp, F Sander, M. Demircan, L Kamolz
Keywords: Lactate, synthetic polylactide membranes, TRPV Channel, SupraSDRM® CW, Suprathel®, angiogenesis, wound healing, pain reduction, tissue neogenesis,
Objectives:
Burns and Wound treatment with polylactide membranes has a long history dating back to 1998. Over the years, it has shown many significant positive effects. Undisturbed wound healing and effective pain relief, dressing changes, and a reduced number of skin grafts in the case of partial-deep burns together with rapid stabilization of the patient come to the fore. In addition, recent results combined with previous results updated the understanding of the mechanism of action.
Methods:
David Julius and Ardem Papapotian received the 2021 Nobel Prize in Medicine for work on TRPV and TRPM ion channels and their impact on pain perception. The influence of these channels on pain and activation of the burn cascade is presented. Lactate can block these channels and influence pain perception and wound healing. Mechanisms and methods of topically applied lactate and the influence on wound healing are presented.
Results:
The thermally activated TRPV channels initiate pain and influence cell death through Ca++ accumulation and increased sodium influx. Cell changes release DAMPs, and via TLRs, P2X, and AIM2 receptors, the entire burn cascade is affected, and the itching[1].
However, TRPV channels can be successfully blocked by lactate, which is not only manifested in the pain-relieving effect[2]. Lactate is an essential co-factor in wound healing, without which adequate angiogenesis cannot occur[3], although it can also be applied topically. In addition, it contributes to the normalization of the wound pH and thus to the reduction of excessive matrix metalloproteinase activity. Lactate adjusts wound pH to optimal growth and proliferation for keratinocytes and fibroblasts[4]. The improved vascularization increases local oxygen tension, which increases the ability of leukocytes to kill bacteria oxidatively and reduces the risk of infection[5].
Conclusion:
Lactate and oxygen are essential to wound healing through TRPV channel blockage, pH adjustment, and cytokine induction. Lactate can be used systemically or topically. The release of lactate can be controlled in terms of amount and duration by the type of membranes used.
[1] Morgan M, Deuis JR, Frøsig-Jørgensen M, Lewis RJ, Cabot PJ, Gray PD, et al. Burn pain: A systematic and critical review of epidemiology, pathophysiology, and treatment. Pain Med (United States) 2018;19:708-34. https://doi.org/10.1093/pm/pnx228.
[2] de la Roche J, Walther I, Leonow W, Hage A, Eberhardt M, Fischer M, et al. Lactate is a potent inhibitor of the capsaicin receptor TRPV1. Sci Rep 2016;6:36740. https://doi.org/10.1038/srep36740.
[3] Hunt TK, Aslam R, Hussain Z, Beckert S. Lactate, with oxygen, incites angiogenesis. Adv. Exp. Med. Biol., vol. 614, 2008, p. 73-80. https://doi.org/10.1007/978-0-387-74911-2_9.
[4] Strohal R, Mittlböck M, Hämmerle G. The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study. Adv Ski Wound Care 2018;31:163-71. https://doi.org/10.1097/01.ASW.0000530687.23867.bd.
[5] All DB. Wound Hypoxia and Acidosis Limit Neutrophil Bacterial Killing Mechanisms. Arch Surg 1997;132:991. https://doi.org/10.1001/archsurg.1997.01430330057009.

**The Effect of Lactate on Pain, Oxygenation, and Wound Healing**
H Haller, M Rapp, F Sander, M. Demircan, L Kamolz
Keywords: Lactate, synthetic polylactide membranes, TRPV Channel, SupraSDRM® CW, Suprathel®, angiogenesis, wound healing, pain reduction, tissue neogenesis,
Objectives:
Burns and Wound treatment with polylactide membranes has a long history dating back to 1998. Over the years, it has shown many significant positive effects. Undisturbed wound healing and effective pain relief, dressing changes, and a reduced number of skin grafts in the case of partial-deep burns together with rapid stabilization of the patient come to the fore. In addition, recent results combined with previous results updated the understanding of the mechanism of action.
Methods:
David Julius and Ardem Papapotian received the 2021 Nobel Prize in Medicine for work on TRPV and TRPM ion channels and their impact on pain perception. The influence of these channels on pain and activation of the burn cascade is presented. Lactate can block these channels and influence pain perception and wound healing. Mechanisms and methods of topically applied lactate and the influence on wound healing are presented.
Results:
The thermally activated TRPV channels initiate pain and influence cell death through Ca++ accumulation and increased sodium influx. Cell changes release DAMPs, and via TLRs, P2X, and AIM2 receptors, the entire burn cascade is affected, and the itching[1].
However, TRPV channels can be successfully blocked by lactate, which is not only manifested in the pain-relieving effect[2]. Lactate is an essential co-factor in wound healing, without which adequate angiogenesis cannot occur[3], although it can also be applied topically. In addition, it contributes to the normalization of the wound pH and thus to the reduction of excessive matrix metalloproteinase activity. Lactate adjusts wound pH to optimal growth and proliferation for keratinocytes and fibroblasts[4]. The improved vascularization increases local oxygen tension, which increases the ability of leukocytes to kill bacteria oxidatively and reduces the risk of infection[5].
Conclusion:
Lactate and oxygen are essential to wound healing through TRPV channel blockage, pH adjustment, and cytokine induction. Lactate can be used systemically or topically. The release of lactate can be controlled in terms of amount and duration by the type of membranes used.
[1] Morgan M, Deuis JR, Frøsig-Jørgensen M, Lewis RJ, Cabot PJ, Gray PD, et al. Burn pain: A systematic and critical review of epidemiology, pathophysiology, and treatment. Pain Med (United States) 2018;19:708-34. https://doi.org/10.1093/pm/pnx228.
[2] de la Roche J, Walther I, Leonow W, Hage A, Eberhardt M, Fischer M, et al. Lactate is a potent inhibitor of the capsaicin receptor TRPV1. Sci Rep 2016;6:36740. https://doi.org/10.1038/srep36740.
[3] Hunt TK, Aslam R, Hussain Z, Beckert S. Lactate, with oxygen, incites angiogenesis. Adv. Exp. Med. Biol., vol. 614, 2008, p. 73-80. https://doi.org/10.1007/978-0-387-74911-2_9.
[4] Strohal R, Mittlböck M, Hämmerle G. The Management of Critically Colonized and Locally Infected Leg Ulcers with an Acid-Oxidizing Solution: A Pilot Study. Adv Ski Wound Care 2018;31:163-71. https://doi.org/10.1097/01.ASW.0000530687.23867.bd.
[5] All DB. Wound Hypoxia and Acidosis Limit Neutrophil Bacterial Killing Mechanisms. Arch Surg 1997;132:991. [https://doi.org/10.1001/archsurg.1997.01430330057009](https://doi.org/10.1001/archsurg.1997.01430330057009).

P.144 The effect of lactate on pain, oxygenation, and wound healing

Dear friends and colleagues,

We will be pleased to welcome you in Turin (Italy) for the 19th European Burns Association´s Congress in 2022. Italy is honored to hold the meeting of the European Burns Association for the second time, after Verona in 1995. Turin is easily reachable from everywhere in Europe, either travelling by car, train or choosing flight connections. During the meeting, held in the renewed industrial center of the main Italian historical automotive factory (i.e. Lingotto-FIAT), we will meet international burn specialists, focusing on standards of care, progresses in burn treatment, strategies to face disaster situations, with a special attention to education of younger colleagues. However, in your spare time, you might enjoy the sweet days of Italian late summer, simply wandering in the green parks and gardens along the two rivers which cross the city, or you might decide to discover the numerous art galleries, churches, palaces, libraries, walking across elegant squares and large boulevards, passing through centuries of art and history; finally, you may choose to immerse yourself in some of the most exciting museum experiences, such as the Cinema Museum and the Turin’s Egyptian museum.

Looking forward to seeing you all in Turin for the 19th European Association´s Congress in 2022!
Maurizio Stella, Congress President, Turin Burn Centre