Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury

Heinsinger, Nicolette M.; Spagnuolo, Gabrielle; Allahyari, R. Vivian; Galer, Simon; Fox, Traci B.; Jaffe, David A.; Thomas, Samantha J.; Iacovitti, Lorraine; Lepore, Angelo C.

doi:10.1016/j.expneurol.2020.113468

Cited by 16 publications

(19 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Laminectomy-only uninjured controls received identical surgeries but did not receive a contusion. While we do not present in the current study functional data from these cervical contusion SCI mice showing the effects of the injury on various NP-related behaviors, we have repeatedly demonstrated that this exact same mouse unilateral C5/6 contusion model reproducibly produces at-level (in the forepaw plantar surface) thermal hyperalgesia and mechanical allodynia in every mouse tested (Heinsinger et al, 2020;Brown, Falnikar et al, 2021). In addition, these NP-related thermal and mechanical phenotypes persist in every mouse until chronic time points postinjury.…”

Section: Sci Surgeriesmentioning

confidence: 58%

“…Tamoxifen administration and peripheral stimulation paradigms Tamoxifen (MilliporeSigma) was dissolved to a concentration of 1 mg/ 10 ml and was delivered via intraperitoneal injection with an insulin syringe 1Â per day for 2 d (160 mg/g bodyweight). Our SCI paradigm causes mechanical allodynia (decreased paw withdrawal threshold in response to a previously innocuous mechanical stimulus; Heinsinger et al, 2020;Brown et al, 2021). Ipsilateral forepaw withdrawal threshold for intact and laminectomy-only mice is ;1.5 g of force using von Frey filaments, while the paw withdrawal threshold of cervical contusion SCI mice is ;0.1 g (Heinsinger et al, 2020;Brown et al, 2021).…”

Section: Sci Surgeriesmentioning

confidence: 99%

“…Using TRAP2 mice, we delivered a clinically relevant cervical hemi-contusion SCI, which we have previously reported induces multiple forms of persistent at-level and below-level NP-related behaviors, including mechanical allodynia and thermal hyperalgesia consistently in all injured mice (Putatunda et al, 2014;Watson et al, 2014;Ritter et al, 2015;Falnikar et al, 2016;Heinsinger et al, 2020;Brown et al, 2021). We used this paradigm to explore SCI-induced activation changes in three neuronal population groups relevant to pain processing: interneurons of the cervical DH and lumbar DH, DH projection neurons of the cervical spinal cord, and neurons in several pain-relevant supraspinal areas (including those that receive direct projections from DH).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential Activation of Pain Circuitry Neuron Populations in a Mouse Model of Spinal Cord Injury-Induced Neuropathic Pain

et al. 2022

View full text Add to dashboard Cite

Neuropathic pain (NP) is one of the most common and debilitating comorbidities of spinal cord injury (SCI). Current therapies are often ineffective due in part to an incomplete understanding of underlying pathogenic mechanisms. In particular, it remains unclear how SCI leads to dysfunction in the excitability of nociceptive circuitry. The immediate early gene c-Fos has long been used in pain processing locations as a marker of neuronal activation. We employed a mouse reporter line with fospromoter driven Cre-recombinase to define neuronal activity changes in relevant pain circuitry locations following cervical spinal cord level (C)5/6 contusion (using both females and males), a SCI model that results in multiple forms of persistent NP-related behavior. SCI significantly increased activation of cervical dorsal horn (DH) projection neurons, as well as induced a selective reduction in the activation of a specific DH projection neuron subpopulation that innervates the periaqueductal gray (PAG), an important brain region involved in descending inhibitory modulation of DH pain transmission. SCI also increased the activation of both protein kinase C (PKC)c and calretinin excitatory DH interneuron populations. Interestingly, SCI promoted a significant decrease in the activation selectively of neuronal nitric oxide synthase (nNOS)-expressing inhibitory interneurons of cervical DH. In addition, SCI altered activation of various supraspinal neuron populations associated with pain processing, including a large increase in thalamus and a significant decrease in PAG. These findings reveal a complex and diverse set of SCI-induced neuron activity changes across the pain circuitry neuraxis. Moving forward, these results can be used to inform therapeutic targeting of defined neuronal populations in NP.

show abstract

Section: Sci Surgeriesmentioning

confidence: 58%

Section: Sci Surgeriesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Activation of Pain Circuitry Neuron Populations in a Mouse Model of Spinal Cord Injury-Induced Neuropathic Pain

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The use of non-evoked pain measures in preclinical models helps to bridge this gap, as spontaneous pain measures are more closely related to the subjective nature of pain than measures of nociception (37,52). Facial grimacing has been used to assess affective components of pain across multiple pain models, including migraine and post-surgical pain, and is often used to assess the efficacy of analgesics (53)(54)(55)(56). Even in studies of spontaneous pain using animal models, interpretation of rodent behaviors has to be considered in the context of prey behavior, as mice are prone to adjusting their behavior for survival (37).…”

Section: Discussion: (1496 Words)mentioning

confidence: 99%

Translating outcomes from the clinical setting to preclinical models: chronic pain and functionality in chronic musculoskeletal pain

Lenert

Gomez

Lane

et al. 2021

Preprint

View full text Add to dashboard Cite

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), tenderness, and fatigue, which interferes with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for pain and muscle function in a preclinical model of CWP. We assessed correlations between pain behaviors and muscle function in a preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between outcomes existed in both settings, for usability of clinical assays in model systems. For preclinical measures, the acidic saline model of FM which induces widespread muscle pain, was used in adult female mice. Two gastrocnemius injections of acidic or physiological pH saline were given following baseline measures, five days apart. An array of adapted pain measures and functional assays were assessed for three weeks. For clinical measures, pain and functional assays were assessed in adult women with FM. For both preclinical and clinical outcomes, movement-evoked pain (MEP) was associated with mechanical pain sensitivity. Mechanical sensitivity was correlated to shifts in weight-bearing preclinically and was predictive of functionality in patients. Preclinically, it is imperative to expand how the field assesses pain behaviors when studying multi- symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models.SummaryPreclinical assessments of chronic musculoskeletal pain recapitulate several outcome measures for clinical assessment of patients with FM, particularly prolonged resting pain, and MEP.

show abstract

“…During more common procedures, such as intraperitoneal administration of substances (e.g., CCl4 and oil as a control group), Erns et al ( 174 ) reported that orbital narrowing was the most observed FAU in the MGS in mice after the intraperitoneal injection of CCl4, demonstrating that MGS can detect pain depending on the agent administered. Likewise, Heinsinger et al ( 175 ) mentions that in murine models of cervical spinal cord injury, the nose and cheek bulge, orbital narrowing, and change of ear position are the most obvious FAU after 2 weeks of cervical contusion. This information does not only show the applicability of the grimace scales and FAU to pain recognition but is also an alternative to decide an analgesic approach for laboratory animals.…”

Section: Clinical Applications Of Facial Expressions In Distinct Expe...mentioning

confidence: 99%

The neurobiology of pain and facial movements in rodents: Clinical applications and current research

et al. 2022

View full text Add to dashboard Cite

One of the most controversial aspects of the use of animals in science is the production of pain. Pain is a central ethical concern. The activation of neural pathways involved in the pain response has physiological, endocrine, and behavioral consequences, that can affect both the health and welfare of the animals, as well as the validity of research. The strategy to prevent these consequences requires understanding of the nociception process, pain itself, and how assessment can be performed using validated, non-invasive methods. The study of facial expressions related to pain has undergone considerable study with the finding that certain movements of the facial muscles (called facial action units) are associated with the presence and intensity of pain. This review, focused on rodents, discusses the neurobiology of facial expressions, clinical applications, and current research designed to better understand pain and the nociceptive pathway as a strategy for implementing refinement in biomedical research.

show abstract

Facial grimace testing as an assay of neuropathic pain-related behavior in a mouse model of cervical spinal cord injury

Cited by 16 publications

References 11 publications

Differential Activation of Pain Circuitry Neuron Populations in a Mouse Model of Spinal Cord Injury-Induced Neuropathic Pain

Differential Activation of Pain Circuitry Neuron Populations in a Mouse Model of Spinal Cord Injury-Induced Neuropathic Pain

Translating outcomes from the clinical setting to preclinical models: chronic pain and functionality in chronic musculoskeletal pain

The neurobiology of pain and facial movements in rodents: Clinical applications and current research

Contact Info

Product

Resources

About