Gait analysis and weight bearing in pre-clinical joint pain research

Möller, Kristina Ängeby; Svärd, Heta; Suominen, Anni; Immonen, Jarmo; Holappa, Johanna; Stenfors, Carina

doi:10.1016/j.jneumeth.2017.04.011

Cited by 28 publications

(20 citation statements)

References 48 publications

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“…Motor behavior was assessed using the CatWalk system (Noldus Information Technology, The Netherlands) as previously described (Angeby Moller et al, 2018). Briefly, 1-year old mice of both sexes were habituated to the room for 30 min and then allowed to cross the Catwalk system three times.…”

Section: Motor and Sensory Behavioral Testsmentioning

confidence: 99%

Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end‐plate innervation

Bouçanova

Pollmeier

Sándor

et al. 2020

Glia

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Recent studies in neuron-glial metabolic coupling have shown that, in the CNS, astrocytes and oligodendrocytes support neurons with energy-rich lactate/pyruvate via monocarboxylate transporters (MCTs). The presence of such transporters in the PNS, in both Schwann cells and neurons, has prompted us to question if a similar interaction may be present. Here we describe the generation and characterization of conditional knockout mouse models where MCT1 or MCT4 is specifically deleted in Schwann cells (named MCT1 and MCT4 cKO). We show that MCT1 cKO and MCT4 cKO mice develop normally and that myelin in the PNS is preserved. However, MCT1 expressed by Schwann cells is necessary for long-term maintenance of motor end-plate integrity as revealed by disrupted neuromuscular innervation in mutant mice, while MCT4 appears largely dispensable for the support of motor neurons. Concomitant to detected structural alterations, lumbar motor neurons from MCT1 cKO mice show transcriptional changes affecting cytoskeletal components, transcriptional regulators, and mitochondria related transcripts, among others. Together, our data indicate that MCT1 plays a role in Schwann cell-mediated maintenance of motor end-plate innervation thus providing further insight into the emerging picture of the biology of the axon-glia metabolic crosstalk.

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Section: Motor and Sensory Behavioral Testsmentioning

confidence: 99%

Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end‐plate innervation

Bouçanova

Pollmeier

Sándor

et al. 2020

Glia

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“…In our study we observed a strong inhibition on mechanical allodynia upon primary afferent silencing, and a milder effect on weight bearing. In comparison to static weight bearing paradigms, including incapacitance tests, experimental rodent models can freely explore the testing chambers, the overall measurements encompass natural locomotive behaviours and gait (66). Of note, our pharmacological interventions target primary afferents of the nociceptive subclasses.…”

Section: Discussionmentioning

confidence: 99%

Role of Primary Afferents in Arthritis Induced Spinal Microglial Reactivity

et al. 2021

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Increased afferent input resulting from painful injury augments the activity of central nociceptive circuits via both neuron-neuron and neuron-glia interactions. Microglia, resident immune cells of the central nervous system (CNS), play a crucial role in the pathogenesis of chronic pain. This study provides a framework for understanding how peripheral joint injury signals the CNS to engage spinal microglial responses. During the first week of monosodium iodoacetate (MIA)-induced knee joint injury in male rats, inflammatory and neuropathic pain were characterized by increased firing of peripheral joint afferents. This increased peripheral afferent activity was accompanied by increased Iba1 immunoreactivity within the spinal dorsal horn indicating microglial activation. Pharmacological silencing of C and A afferents with co-injections of QX-314 and bupivacaine, capsaicin, or flagellin prevented the development of mechanical allodynia and spinal microglial activity after MIA injection. Elevated levels of ATP in the cerebrospinal fluid (CSF) and increased expression of the ATP transporter vesicular nucleotide transporter (VNUT) in the ipsilateral spinal dorsal horn were also observed after MIA injections. Selective silencing of primary joint afferents subsequently inhibited ATP release into the CSF. Furthermore, increased spinal microglial reactivity, and alleviation of MIA-induced arthralgia with co-administration of QX-314 with bupivacaine were recapitulated in female rats. Our results demonstrate that early peripheral joint injury activates joint nociceptors, which triggers a central spinal microglial response. Elevation of ATP in the CSF, and spinal expression of VNUT suggest ATP signaling may modulate communication between sensory neurons and spinal microglia at 2 weeks of joint degeneration.

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“…During the last decade, novel methods have been developed for evaluating spontaneous activity in rodents before and after induction of a pain including dynamic weight bearing, place preference on plate with temperature gradient, catwalk and facial assessments 135 . These methods contribute to our understanding of rodent behavior and have been used to evaluate therapies to alleviate pain 136,137 ; similar methods have been used in pigs 73,90,104,122 . Motivational tasks are also available for pigs, such as judgement bias, discrimination, gambling tasks 138 and the marshmallow test 139 .…”

Section: Discussionmentioning

confidence: 99%