Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

BACKGROUND: The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1) and ASIC3 (acid sensing ion channel-3) respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. METHODS: The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons), and their soma diameter was measured. RESULTS: Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1(+)/ASIC3(- )neurons with probably slow conduction velocity (small soma, neurofilament 68-negative) were significantly more frequent among pleural (35%) than pulmonary afferents (20%). TRPV1(+)/ASIC3(+ )neurons amounted to 14 and 10% respectively. TRPV1(-)/ASIC3(+ )neurons made up between 44% (lung) and 48% (pleura) of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive). CONCLUSION: Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1(+)/ASIC3(- )neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli

Excitability of Aβ sensory neurons is altered in an animal model of peripheral neuropathy

<p>Abstract</p> <p>Background</p> <p>Causes of neuropathic pain following nerve injury remain unclear, limiting the development of mechanism-based therapeutic approaches. Animal models have provided some directions, but little is known about the specific sensory neurons that undergo changes in such a way as to induce and maintain activation of sensory pain pathways. Our previous studies implicated changes in the Aβ, normally non-nociceptive neurons in activating spinal nociceptive neurons in a cuff-induced animal model of neuropathic pain and the present study was directed specifically at determining any change in excitability of these neurons. Thus, the present study aimed at recording intracellularly from Aβ-fiber dorsal root ganglion (DRG) neurons and determining excitability of the peripheral receptive field, of the cell body and of the dorsal roots.</p> <p>Methods</p> <p>A peripheral neuropathy was induced in Sprague Dawley rats by inserting two thin polyethylene cuffs around the right sciatic nerve. All animals were confirmed to exhibit tactile hypersensitivity to von Frey filaments three weeks later, before the acute electrophysiological experiments. Under stable intracellular recording conditions neurons were classified functionally on the basis of their response to natural activation of their peripheral receptive field. In addition, conduction velocity of the dorsal roots, configuration of the action potential and rate of adaptation to stimulation were also criteria for classification. Excitability was measured as the threshold to activation of the peripheral receptive field, the response to intracellular injection of depolarizing current into the soma and the response to electrical stimulation of the dorsal roots.</p> <p>Results</p> <p>In control animals mechanical thresholds of all neurons were within normal ranges. Aβ DRG neurons in neuropathic rats demonstrated a mean mechanical threshold to receptive field stimulation that were significantly lower than in control rats, a prolonged discharge following this stimulation, a decreased activation threshold and a greater response to depolarizing current injection into the soma, as well as a longer refractory interval and delayed response to paired pulse electrical stimulation of the dorsal roots.</p> <p>Conclusions</p> <p>The present study has demonstrated changes in functionally classified Aβ low threshold and high threshold DRG neurons in a nerve intact animal model of peripheral neuropathy that demonstrates nociceptive responses to normally innocuous cutaneous stimuli, much the same as is observed in humans with neuropathic pain. We demonstrate further that the peripheral receptive fields of these neurons are more excitable, as are the somata. However, the dorsal roots exhibit a decrease in excitability. Thus, if these neurons participate in neuropathic pain this differential change in excitability may have implications in the peripheral drive that induces central sensitization, at least in animal models of peripheral neuropathic pain, and Aβ sensory neurons may thus contribute to allodynia and spontaneous pain following peripheral nerve injury in humans.</p

Functional Changes in Muscle Afferent Neurones in an Osteoarthritis Model: Implications for Impaired Proprioceptive Performance

Impaired proprioceptive performance is a significant clinical issue for many who suffer osteoarthritis (OA) and is a risk factor for falls and other liabilities. This study was designed to evaluate weight-bearing distribution in a rat model of OA and to determine whether changes also occur in muscle afferent neurones.Intracellular recordings were made in functionally identified dorsal root ganglion neurones in acute electrophysiological experiments on the anaesthetized animal following measurements of hind limb weight bearing in the incapacitance test. OA rats but not naïve control rats stood with less weight on the ipsilateral hind leg (P = 0.02). In the acute electrophysiological experiments that followed weight bearing measurements, action potentials (AP) elicited by electrical stimulation of the dorsal roots differed in OA rats, including longer AP duration (P = 0.006), slower rise time (P = 0.001) and slower maximum rising rate (P = 0.03). Depolarizing intracellular current injection elicited more APs in models than in naïve muscle afferent neurones (P = 0.01) indicating greater excitability. Axonal conduction velocity in model animals was slower (P = 0.04).The present study demonstrates changes in hind limb stance accompanied by changes in the functional properties of muscle afferent neurones in this derangement model of OA. This may provide a possible avenue to explore mechanisms underlying the impaired proprioceptive performance and perhaps other sensory disorders in people with OA

A pilot study to determine whether repeated post-exercise cryotherapy exposure augments physiological and perceptual responses to cold

INTRODUCTION: Cold water immersion (CWI) is a popular recovery strategy employed by athletes attempting to expedite recovery following strenuous exercise. Cold exposure is known to upregulate the production of the potent vasoconstrictor endothelin-1 (ET-1) which could augment the cooling potential, and efficacy, of CWI over time. Therefore, the aim of this study was to investigate the influence of repeated post exercise CWI on circulating ET-1 and perceptions of thermal comfort and sensation. METHODS: Seven resistance trained males (age 26 ± 6 years; height 1.71 ± 0.06 m; mass 74.8 ± 8.3 kg) completed an 8 week lower body resistance training program. Participants completed 2 training sessions per week with each session followed by a CWI protocol (10 min at 10°C ± 0.5°). At the first and last training session (sessions 1 and 16 respectively) blood samples were taken to analyse circulating levels of ET-1, and measures of thermal sensation and comfort were recorded after 5 minutes of the post-exercise CWI protocol. Participants were asked to rate their thermal sensation on a nine point standard scale. Participants were asked ‘How are you feeling now?’ and responded by pointing to the scale where 4 = very hot, 3 = hot, 2 = warm, 1 = slightly warm, 0 = neutral, -1 = slightly cool, -2 = cool, -3 = cold and -4 = very cold. Thermal comfort was also assessed using a five-point scale (‘Do you find this,’ 0 =comfortable, 1 = slightly uncomfortable, 2 = uncomfortable, 3 = very uncomfortable, 4 = extremely uncomfortable). Data were analysed using T-tests to assess changes in thermal sensation, thermal comfort and ET-1 from session 1 to 16. RESULTS: The results demonstrated that thermal sensation was significantly increased (t(6) = -2.75, p = 0.03) and thermal comfort was significantly improved (t(6) = 4.07, p = 0.006) from session 1 to session 16. Despite an increase in mean scores from session 1 to 16, there was no statistically significant alteration in ET-1 (t(5) = -0.69, p = 0.52). CONCLUSION: The findings from this study demonstrate that participants felt ‘warmer’ and experienced less discomfort during CWI from session 1 to 16. This indicates that individuals regularly using CWI as a recovery intervention are likely to experience perceptual habituation as a result of repeated exposure. Further investigation is warranted to understand the potential influence of CWI on ET-1 and the impact this may have on peripheral blood flow and skeletal muscle cooling

Cold water immersion offers no functional or perceptual benefit compared to a sham intervention during a resistance training program

Cold water immersion (CWI) is regularly used by athletes as a postexercise recovery strategy, but relatively little is understood about potential training adaptations associated with habitual use. The aim of this study was to investigate the influence of repeated CWI or a sham intervention on adaptations to a lower body resistance training program. Thirteen men (26 +- 6 years; 83.6 +- 15.7 kg) familiar with resistance training were allocated into a CWI (10 minutes at 10˚ C) or sham group and completed 2 x 4-week blocks of lower body resistance training. Subjects completed a total of 16 training sessions (2 x session·week-1), with each session immediately followed by their allocated recovery intervention. Measures of perceptual markers, muscle function, and muscle architecture were recorded at baseline, midpoint, and post-training. Data were analyzed using factorial analysis of variances. The training program resulted in significant increases in muscle fibre pennation angle (p = 0.009), isometric peak force (p = 0.018), and 1/4 squat (p 0.05). There were no differences in perceptual responses between groups. Despite the popularity of CWI as a postexercise recovery intervention, the findings from the present study demonstrated no functional or perceptual benefit compared with a sham intervention during progressive strength and power training. Furthermore, there was no detrimental impact of CWI on morphological adaptations after 16 exposures. These findings are important for athletes and practitioners wishing to use CWI as an acute recovery strategy after training, without blunting potential training adaptations

Cold Water Immersion Offers No Functional or Perceptual Benefit Compared to a Sham Intervention During a Resistance Training Program.

ABSTRACT: Wilson, LJ, Dimitriou, L, Hills, FA, Gondek, MB, van Wyk, A, Turek, V, Rivkin, T, Villiere, A, Jarvis, P, Miller, S, Turner, A, and Cockburn, E. Cold water immersion offers no functional or perceptual benefit compared to a sham intervention during a resistance training program. J Strength Cond Res 35(10): 2720-2727, 2021-Cold water immersion (CWI) is regularly used by athletes as a postexercise recovery strategy, but relatively little is understood about potential training adaptations associated with habitual use. The aim of this study was to investigate the influence of repeated CWI or a sham intervention on adaptations to a lower body resistance training program. Thirteen men (26 ± 6 years; 83.6 ± 15.7 kg) familiar with resistance training were allocated into a CWI (10 minutes at 10° C) or sham group and completed 2 × 4-week blocks of lower body resistance training. Subjects completed a total of 16 training sessions (2 × session·week-1), with each session immediately followed by their allocated recovery intervention. Measures of perceptual markers, muscle function, and muscle architecture were recorded at baseline, midpoint, and post-training. Data were analyzed using factorial analysis of variances. The training program resulted in significant increases in muscle fibre pennation angle (p = 0.009), isometric peak force (p = 0.018), and 1/4 squat (p 0.05). There were no differences in perceptual responses between groups. Despite the popularity of CWI as a postexercise recovery intervention, the findings from the present study demonstrated no functional or perceptual benefit compared with a sham intervention during progressive strength and power training. Furthermore, there was no detrimental impact of CWI on morphological adaptations after 16 exposures. These findings are important for athletes and practitioners wishing to use CWI as an acute recovery strategy after training, without blunting potential training adaptations