Evaluating pain behaviours: Widely used mechanical and thermal methods in rodents

Modi, Akshat D.; Parekh, Anavi; Pancholi, Yajan N.

doi:10.1016/j.bbr.2023.114417

Cited by 10 publications

(5 citation statements)

References 95 publications

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“…Other neuropathic models, like chronic constriction injury (CCI) to the sciatic nerve, have a larger heat hyperalgesia that could be tested for TCF effects. Testing TCF effects on other rodent models of pain would also be informative, such as acute or long-term peripheral inflammatory models, and cancer chemotherapy pain models (54). We did not test the extent to which the affective component of SNI neuropathic pain was being modulated by TCF.…”

Section: Discussionmentioning

confidence: 99%

Long-range action of an HDAC inhibitor treats chronic pain in a spared nerve injury rat model

Centeno,

Alam,

Haldar

et al. 2023

Preprint

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Histone deacetylase inhibitors (HDACi) that modulate epigenetic regulation and are approved for treating rare cancers have, in disease models, also been shown to mitigate neurological conditions, including chronic pain. They are of interest as non-opioid treatments, but achieving long-term efficacy with limited dosing has remained elusive. Here we utilize a triple combination formulation (TCF) comprised of a pan-HDACi vorinostat (Vo at its FDA-approved daily dose of 50mg/Kg), the caging agent 2-hydroxypropyl-β-cyclodextrin (HPBCD) and polyethylene glycol (PEG) known to boost plasma and brain exposure and efficacy of Vo in mice and rats, of various ages, spared nerve injury (SNI) model of chronic neuropathic pain. Administration of the TCF (but not HPBCD and PEG) decreased mechanical allodynia for 4 weeks without antagonizing weight, anxiety, or mobility. This was achieved at less than 1% of the total dose of Vo approved for 4 weeks of tumor treatment and associated with decreased levels of major inflammatory markers and microglia in ipsilateral (but not contralateral) spinal cord regions. A single TCF injection was sufficient for 3-4 weeks of efficacy: this was mirrored in repeat injections, specific for the injured paw and not seen on sham treatment. Pharmacodynamics in an SNI mouse model suggested pain relief was sustained for days to weeks after Vo elimination. Doubling Vo in a single TCF injection proved effectiveness was limited to male rats, where the response amplitude tripled and remained effective for > 2 months, an efficacy that outperforms all currently available chronic pain pharmacotherapies. Together, these data suggest that through pharmacological modulation of Vo, the TCF enables single-dose effectiveness with extended action, reduces long-term HDACi dosage, and presents excellent potential to develop as a non-opioid treatment option for chronic pain.

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Section: Discussionmentioning

confidence: 99%

Long-range action of an HDAC inhibitor treats chronic pain in a spared nerve injury rat model

Centeno,

Alam,

Haldar

et al. 2023

Preprint

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“…The Hargreave's test is well established and has been described previously 26–29 . Briefly, rats were placed on an elevated, temperature‐controlled surface (model 390 G; IITC) and allowed to acclimate for 5–10 min such that the animals were settled in the cage 27 .…”

Section: Methodsmentioning

confidence: 99%

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation

Buzza,

Tapas,

Zhuo

et al. 2024

Lasers Surg Med

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ObjectivePhotobiomodulation at higher irradiances has great potential as a pain‐alleviating method that selectively inhibits small diameter nerve fibers and corresponding sensory experiences, such as nociception and heat sensation. The longevity and magnitude of these effects as a function of laser irradiation parameters at the nerve was explored.MethodsIn a rodent chronic pain model (spared nerve injury—SNI), light was applied directly at the sural nerve with four delivery schemes: two irradiance levels (7.64 and 2.55 W/cm2) for two durations each, corresponding to either 4.8 or 14.4 J total energy, and the effect on sensory hypersensitivities was evaluated.ResultsAt emitter irradiances of 7.64 W/cm2 (for 240 s), 2.55 W/cm2 (for 720 s), and 7.64 W/cm2 (for 80 s) the heat hypersensitivity was relieved the day following photobiomodulation (PBM) treatment by 37 ± 8.1% (statistically significant, p < 0.001), 26% ± 6% (p = 0.072), and 28 ± 6.1% (statistically significant, p = 0.032), respectively, and all three treatments reduced the hypersensitivity over the course of the experiment (13 days) at a statistically significant level (mixed‐design analysis of variance, p < 0.05). The increases in tissue temperature (5.3 ± 1.0 and 1.3 ± 0.4°C from 33.3°C for the higher and lower power densities, respectively) at the neural target were well below those typically associated with permanent action potential disruption.ConclusionsThe data from this study support the use of direct PBM on nerves of interest to reduce sensitivities associated with small‐diameter fiber activity.

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“…Each of these tests provides unique insights into thermal pain responses, and their combination allows for a more robust assessment of the drug's impact on thermal hypersensitivity. The tail flick test primarily evaluates the spinal reflex withdrawal response to a noxious thermal stimulus, while the hot plate test assesses the response to a more prolonged thermal stimulus involving both spinal and supraspinal mechanisms [ 22 ]. By employing both tests, the authors aimed to capture different aspects of thermal nociceptive processing, providing a more complete picture of the drug's effects on thermal pain perception.…”

Section: Methodsmentioning

confidence: 99%

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

Dirik,

Taşkıran,

Joha

2024

Korean J Pain

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Evaluating pain behaviours: Widely used mechanical and thermal methods in rodents

Cited by 10 publications

References 95 publications

Long-range action of an HDAC inhibitor treats chronic pain in a spared nerve injury rat model

Long-range action of an HDAC inhibitor treats chronic pain in a spared nerve injury rat model

Selective neural inhibition via photobiomodulation alleviates behavioral hypersensitivity associated with small sensory fiber activation

Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

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