Pain modulated by Bothrops snake venoms: Mechanisms of nociceptive signaling and therapeutic perspectives

Cavalcante, Joeliton dos Santos; Júnior, Francisco Assis Nogueira; Jorge, Roberta Jeane Bezerra; Almeida, Cayo

doi:10.1016/j.toxicon.2021.08.016

Cited by 11 publications

(25 citation statements)

References 138 publications

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“…In Bothrops SBEs, pain is usually the first sign to appear and alerts the patient to the situation. This manifestation is present in practically all patients . Even with AVT, pain persists for days in patients with B atrox envenomations and thus requires administration of analgesics .…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox

Carvalho,

Souza,

Melo

et al. 2024

JAMA Intern Med

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ImportanceBothrops venom acts almost immediately at the bite site and causes tissue damage.ObjectiveTo investigate the feasibility and explore the safety and efficacy of low-level laser therapy (LLLT) in reducing the local manifestations of B atrox envenomations.Design, Setting, and ParticipantsThis was a double-blind randomized clinical trial conducted at Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, in Manaus, Brazil. A total of 60 adult participants were included from November 2020 to March 2022, with 30 in each group. Baseline characteristics on admission were similarly distributed between groups. Data analysis was performed from August to December 2022.InterventionThe intervention group received LLLT combined with regular antivenom treatment. The laser used was a gallium arsenide laser with 4 infrared laser emitters and 4 red laser emitters, 4 J/cm2 for 40 seconds at each application point.Main Outcomes and MeasuresFeasibility was assessed by eligibility, recruitment, and retention rates; protocol fidelity; and patients’ acceptability. The primary efficacy outcome of this study was myolysis estimated by the value of creatine kinase (U/L) on the third day of follow-up. Secondary efficacy outcomes were (1) pain intensity, (2) circumference measurement ratio, (3) extent of edema, (4) difference between the bite site temperature and that of the contralateral limb, (5) need for the use of analgesics, (6) frequency of secondary infections, and (7) necrosis. These outcomes were measured 48 hours after admission. Disability assessment was carried out from 4 to 6 months after patients’ discharge. P values for outcomes were adjusted with Bonferroni correction.ResultsA total of 60 patients (mean [SD] age, 43.2 [15.3] years; 8 female individuals [13%] and 52 male individuals [87%]) were included. The study was feasible, and patient retention and acceptability were high. Creatine kinase was significantly lower in the LLLT group (mean [SD], 163.7 [160.0] U/L) 48 hours after admission in relation to the comparator (412.4 [441.3] U/L) (P = .03). Mean (SD) pain intensity (2.9 [2.7] vs 5.0 [2.4]; P = .004), circumference measurement ratio (6.6% [6.6%] vs 17.1% [11.6%]; P &lt; .001), and edema extent (25.8 [15.0] vs 40.1 [22.7] cm; P = .002) were significantly lower in the LLLT group in relation to the comparator. No difference was observed between the groups regarding the mean difference between the bite site temperature and the contralateral limb. Secondary infections, necrosis, disability outcomes, and the frequency of need for analgesics were similar in both groups. No adverse event was observed.Conclusions and RelevanceThe data from this randomized clinical trial suggest that the use of LLLT was feasible and safe in a hospital setting and effective in reducing muscle damage and the local inflammatory process caused by B atrox envenomations.Trial RegistrationBrazilian Registry of Clinical Trials Identifier: RBR-4qw4vf

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Section: Discussionmentioning

confidence: 99%

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox

Carvalho,

Souza,

Melo

et al. 2024

JAMA Intern Med

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“…Bothrops venoms are mostly composed of zinc-dependent metalloproteases (SVMPs), phospholipases A 2 (PLA 2 s), and serine proteases (SVSPs), which in situations of human envenoming, trigger a wide spectrum of pathophysiological manifestations [7,[9][10][11][12][13][14][15], such as pain, edema, blistering, myonecrosis, vascular injury, ischemia, necrosis, blood incoagulability, oxidative stress, bleeding, among others [16][17][18]. Although the wide variability in the venom proteome of Bothrops is recognized, this pattern of local and systemic clinical manifestations is replicated among envenomed patients by species of this genus, which suggests the presence of a shared mechanism of action, which can lead to complications such as intracranial hemorrhage, acute kidney injury, compartment syndromes, and amputations [8,[19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk of Inflammation and Coagulation in Bothrops Snakebite Envenoming: Endogenous Signaling Pathways and Pathophysiology

Cavalcante

Almeida

Santos-Filho

et al. 2023

IJMS

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Snakebite envenoming represents a major health problem in tropical and subtropical countries. Considering the elevated number of accidents and high morbidity and mortality rates, the World Health Organization reclassified this disease to category A of neglected diseases. In Latin America, Bothrops genus snakes are mainly responsible for snakebites in humans, whose pathophysiology is characterized by local and systemic inflammatory and degradative processes, triggering prothrombotic and hemorrhagic events, which lead to various complications, organ damage, tissue loss, amputations, and death. The activation of the multicellular blood system, hemostatic alterations, and activation of the inflammatory response are all well-documented in Bothrops envenomings. However, the interface between inflammation and coagulation is still a neglected issue in the toxinology field. Thromboinflammatory pathways can play a significant role in some of the major complications of snakebite envenoming, such as stroke, venous thromboembolism, and acute kidney injury. In addition to exacerbating inflammation and cell interactions that trigger vaso-occlusion, ischemia–reperfusion processes, and, eventually, organic damage and necrosis. In this review, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet and leukocyte activation, as well as the inflammatory production mediators and induction of innate immune responses, among other mechanisms that are altered by Bothrops venoms.

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“…Human envenoming by venomous animals represents the main neglected health problem in tropical and subtropical countries [ 1 , 2 , 3 , 4 ]. Due to its climatic heterogeneity and different biomes, Brazil harbors a great variety of venomous animals with harmful potential for humans [ 5 , 6 , 7 ]. The therapeutic procedures for envenoming by venomous animals consist of the administration of antivenoms [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Challenges and Opportunities in Clinical Diagnostic Routine of Envenomation Using Blood Plasma Proteomics

Cavalcante

Almeida

Moraes

et al. 2023

Toxins

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Specific and sensitive tools for the diagnosis and monitoring of accidents by venomous animals are urgently needed. Several diagnostic and monitoring assays have been developed; however, they have not yet reached the clinic. This has resulted in late diagnoses, which represents one of the main causes of progression from mild to severe disease. Human blood is a protein-rich biological fluid that is routinely collected in hospital settings for diagnostic purposes, which can translate research progress from the laboratory to the clinic. Although it is a limited view, blood plasma proteins provide information about the clinical picture of envenomation. Proteome disturbances in response to envenomation by venomous animals have been identified, allowing mass spectrometry (MS)-based plasma proteomics to emerge as a tool in a range of clinical diagnostics and disease management that can be applied to cases of venomous animal envenomation. Here, we provide a review of the state of the art on routine laboratory diagnoses of envenomation by snakes, scorpions, bees, and spiders, as well as a review of the diagnostic methods and the challenges encountered. We present the state of the art on clinical proteomics as the standardization of procedures to be performed within and between research laboratories, favoring a more excellent peptide coverage of candidate proteins for biomarkers. Therefore, the selection of a sample type and method of preparation should be very specific and based on the discovery of biomarkers in specific approaches. However, the sample collection protocol (e.g., collection tube type) and the processing procedure of the sample (e.g., clotting temperature, time allowed for clotting, and anticoagulant used) are equally important to eliminate any bias.

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Pain modulated by Bothrops snake venoms: Mechanisms of nociceptive signaling and therapeutic perspectives

Cited by 11 publications

References 138 publications

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox

Photobiomodulation Therapy to Treat Snakebites Caused by Bothrops atrox

Crosstalk of Inflammation and Coagulation in Bothrops Snakebite Envenoming: Endogenous Signaling Pathways and Pathophysiology

Challenges and Opportunities in Clinical Diagnostic Routine of Envenomation Using Blood Plasma Proteomics

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