C57BL/6 substrain differences in formalin-induced pain-like behavioral responses

Ulker, Esad; Caillaud, Martial; Patel, Tulsi; White, Alyssa; Rashid, Danyal; Alqasem, Mashael; Lichtman, Aron H.; Bryant, Camron D.; Damaj, M. Imad

doi:10.1016/j.bbr.2020.112698

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…The discrepancy between these results could be explained by difference in timing of tissue collection, route of administration, and C57BL/6 substrain differences that could affect these results (52). Indeed, we and others recently reported that C57BL/6J and C57BL/6N substrains differ in their responses in acute and tonic pain models (53)(54)(55).…”

Section: Discussionmentioning

confidence: 87%

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

et al. 2021

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Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose limiting, and long-lasting side effect of chemotherapy treatment. Unfortunately, no treatment has proven efficacious for this side effect. Rodent models play a crucial role in the discovery of new mechanisms underlying the initiation, progression, and recovery of CIPN and the potential discovery of new therapeutics. However, there is limited consistency in the dose, the sex, age, and genetic background of the animal used in these studies and the outcome measures used in evaluation of CIPN rely primarily on noxious and reflexive measures. The main objective of this study was to provide a comprehensive and systematic characterization of oxaliplatin-induced peripheral neuropathy in mice by using a battery of behavioral, sensory, electrophysiological, and morphometric measures in both sexes of the two widely used strains of mice, C57BL/6J and BALB/cJ. Mice received intraperitoneal injections of 3 or 30 mg/kg cumulative doses of oxaliplatin over the course of 2 weeks. Both doses induced long-term and time-dependent mechanical and cold hypersensitivity. Our results show that 30 mg/kg oxaliplatin reduced the locomotor activity in C57BL/6J mice, and C57BL/6J females showed anxiety-like behavior one-week post completion of treatment. In the same dose group, BALB/cJ males and females sustained a larger decrease in sucrose preference than either male or female C57BL/6J mice. Both strains failed to show significant changes in burrowing and nesting behaviors. Two clinically relevant assessments of changes to the peripheral nerve fibers, nerve conduction and intraepidermal nerve fiber density (IENFD) were evaluated. Only BALB/cJ females showed significant reduction in the nerve conduction amplitude 1 week after 30 mg/kg oxaliplatin regimen. Moreover, this dose of the chemo agent reduced the IENF density in both sexes and strains. Our findings suggest that mouse strain, sex, and assay type should be carefully considered when assessing the effects of oxaliplatin and potential therapeutic interventions.

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Section: Discussionmentioning

confidence: 87%

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

et al. 2021

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“…6C and 6G ). Of note, we recognize that effects on nociception observed in our animals may be impacted by the mixed NJ strain background, as B6N and B6J mice are known to exhibit divergent behavior in some pain models (Ulker et al, 2020). Nonetheless, these findings show that Scrn3 KO mice are selectively deficient in thermal nociception consistent with that observed in the Drosophila screen, indicating that the Scrn3 gene has a conserved functional role across species.…”

Section: Resultsmentioning

confidence: 99%

“…Alkynylated analogs of covalent drugs compatible with late-stage biorthogonal click chemistry developed for ABPP and chemical proteomics approaches has proven powerful for identifying drug targets in vivo (Speers et al, 2003;Niphakis et al, 2012;Niphakis and Cravatt, 2014;Zuhl et al, 2016;Niessen et al, 2017;van Esbroeck et al, 2017;Whitby et al, 2017;Caneque et al, 2018). Here, we applied our alkynylated PHZ probe (PHZyne) to directly visualize, identify and quantify reactive and high-occupancy on-and off-targets of PHZ in mouse tissues.…”

Section: A Clickable Probe To Directly Evaluate Phz-modified Proteins...mentioning

confidence: 99%

Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception

Bustin¹,

Shishikura²,

Chen

et al. 2023

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Chemical platforms that facilitate both the identification and elucidation of new areas for therapeutic development are necessary but lacking. Activity-based protein profiling (ABPP) leverages active site-directed chemical probes as target discovery tools that resolve activity from expression and immediately marry the targets identified with lead compounds for drug design. However, this approach has traditionally focused on predictable and intrinsic enzyme functionality. Here, we applied our activity-based proteomics discovery platform to map non-encoded and post-translationally acquired enzyme functionalities (e.g. cofactors) in vivo using chemical probes that exploit the nucleophilic hydrazine pharmacophores found in a classic antidepressant drug (e.g. phenelzine, Nardil ®). We show the probes are in vivo active and can map proteome-wide tissue-specific target engagement of the drug. In addition to engaging targets (flavoenzymes monoamine oxidase A/B) that are associated with the known therapeutic mechanism as well as several other members of the flavoenzyme family, the probes captured the previously discovered N-terminal glyoxylyl (Glox) group of Secernin-3 (SCRN3) in vivo through a divergent mechanism, indicating this functional feature has biochemical activity in the brain. SCRN3 protein is ubiquitously expressed in the brain, yet gene expression is regulated by inflammatory stimuli. In an inflammatory pain mouse model, behavioral assessment of nociception showed Scrn3 male knockout mice selectively exhibited impaired thermal nociceptive sensitivity. Our study provides a guided workflow to entangle molecular (off)targets and pharmacological mechanisms for therapeutic development.

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“…Mechanical hypersensitivity was determined using the von Frey filaments test as previously reported [27].…”

Section: Mechanical Sensitivity: Von Frey Filaments Testmentioning

confidence: 99%

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors

et al. 2022

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Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.

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C57BL/6 substrain differences in formalin-induced pain-like behavioral responses

Cited by 14 publications

References 23 publications

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice

Phenelzine-based probes reveal Secernin-3 is involved in thermal nociception

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors

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