Strain and Sex Influence on Pain Sensitivity after Plantar Incision in the Mouse

Banik, Ratan K.; Woo, Young Cheol; Park, Soo Seog; Brennan, Timothy J.

doi:10.1097/00000542-200612000-00025

Cited by 82 publications

(74 citation statements)

References 31 publications

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“…For our first model, we used intraplantar injection of CFA, which consists of a mixture of paraffin oil (85% vol/vol), mannide monooleate (15% vol/vol), and heatkilled Mycobacteria tuberculosis (1 mg/mL), and is an immunological adjuvant (13)(14)(15). Second, we chose a modified plantar incision (injury to the skin and underlying muscle) to model sterile tissue injury-based inflammation (16)(17)(18). Both of these models evoke strong pain-like behavior in rodents (17,19), and are widely used for preclinical mechanism-based and pharmacological studies.…”

Section: Resultsmentioning

confidence: 99%

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CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

148

135

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Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant-and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G + CD11b + neutrophils and T-cell receptor (TCR) β + T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b + Ly6G − myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2 + Ly6C hi ) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b + Ly6G − myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.pain | inflammation | cytokines | monocytes | macrophages

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Section: Resultsmentioning

confidence: 99%

“…Second, we chose a modified plantar incision (injury to the skin and underlying muscle) to model sterile tissue injury-based inflammation (16)(17)(18). Both of these models evoke strong pain-like behavior in rodents (17,19), and are widely used for preclinical mechanism-based and pharmacological studies.…”

Section: Resultsmentioning

confidence: 99%

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

148

135

View full text Add to dashboard Cite

show abstract

“…First, mechanical sensitization of low threshold A-and C-fibers was present after incision. The 10 to 20 mN forces needed to excite these sensitized fibers correspond to the force evoking paw withdrawal in 80 to 90% of mice incised one day after incision [4]. Before incision, these mice were largely unresponsive to these forces.…”

Section: Discussionmentioning

confidence: 99%

“…After loss of the righting reflex, anesthesia was maintained by administrating 2-3% isoflurane in air through a tightly fitting mask. An 8-mm longitudinal incision was made with a number 11 blade through the skin, fascia, and muscle of the right hind paw as described previously [4] and modified from Pogatzki and Raja (2003). The skin was apposed with two single sutures of 6-0 nylon, and the wound site was covered with triple antibiotic ointment.…”

Section: Plantar Incisionmentioning

confidence: 99%

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Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation ☆

Banik

Brennan

2008

Pain

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In this study we recorded activity from afferent fibers innervating the mouse plantar skin, the same region evaluated in pain behavior experiments. We compared responses of afferents from incised and unincised hind paw skin. The plantar skin together with attached medial and lateral plantar nerves were dissected until they could be completely removed intact and placed in an organ bath chamber continuously perfused with oxygenated Kreb's solution and temperature maintained at 32°C. Afferent nerve activities to feedback controlled mechanical and heat stimuli and cooling were recorded. Eighty-five single A and C-fiber afferents were recorded, 42 from control and the remainder from incised animals. A greater proportion of C-fibers (11/34) from incised skin had spontaneous activity than the unincised preparation (2/32). The mechanical thresholds of both A and C-fiber units were not different between control and incised groups but the responses to suprathreshold mechanical stimulation were increased in low threshold A and C-fibers. The greatest change in heat sensitivity was apparent when multi-fiber total activity was measured; threshold was reduced, total spikes were greater and the peak discharge frequency was increased. In summary, feedback-controlled stimulation identified mechanical sensitization after incision in an in vitro preparation. Few fibers were excited by cooling. Heat sensitization of primary afferents was more prominent when activities of unclassified afferents are included. The preparation allows us to study afferent function of the same tissue that is examined for in vivo pain behavior assays in mice.

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Maternal separation affects the electrophysiological properties of Aδ‐fibres and nociceptive behaviours in male and female mice

Paniagua

Girón

Goicoechea

et al. 2020

Intl J of Devlp Neuroscience

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Aim: Early life adverse effects have been associated with an increased risk of suffering pain syndromes in adulthood. Although animal models are of great importance to study modifications of pain sensitivity, up to date the results obtained are contradicting due to the varied methodologies used. Therefore, the aim of the present study was to characterise, as a whole, possible modifications in visceral and somatic nociceptive responses in male and female ICR mice, submitted to two different protocols of maternal separation (MS), and possible modifications in the electrophysiological properties of peripheral nociceptive Aδ-primary afferents. Main methods: Male and female mice were submitted to 3 or 4-8 hr of daily MS from postnatal day (PND) 2-17 and early weaned. On PND 67 von Frey, hot plate and writhing tests were performed. Afterwards electrophysiological recordings were carried out, using the in vitro skin-saphenous nerve preparation in males. Key findings: The short separation protocol of MS did not modify nociceptive sensitivity; but when mice were separated from their dams for the long separation, mechanical pain thresholds were modified in male and female mice and visceral nociception was increased in female mice. Electrophysiological recordings showed that cutaneous Aδ-fibres were sensitised and their mechanotransduction properties were altered in both MS protocols. Significance: Although MS increases the activity and the mechanosensitivity of cutaneous Aδ-afferent fibres at both short and long periods of separation, only the longer interval of time induces nociceptive sensitivity alterations during adulthood. These results highlight the possible influence of a stress free environment during childhood to reduce nociceptive alterations in adulthood.

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Strain and Sex Influence on Pain Sensitivity after Plantar Incision in the Mouse

Cited by 82 publications

References 31 publications

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation ☆

Maternal separation affects the electrophysiological properties of Aδ‐fibres and nociceptive behaviours in male and female mice

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Strain and Sex Influence on Pain Sensitivity after Plantar Incision in the Mouse

Cited by 82 publications

References 31 publications

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation ☆

Maternal separation affects the electrophysiological properties of Aδ‐fibres and nociceptive behaviours in male and female mice

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CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity