Suppression of ventral hippocampal CA1 pyramidal neuronal activities enhances water intake

Thirst is an important interoceptive response and drives water consumption. The hippocampus actively modulates food intake and energy metabolism, but direct evidence for the exact role of the hippocampus in modulating drinking behaviors is lacking. We observed decreased number of c-Fos-positive neurons in the ventral hippocampal CA1 (vCA1) after water restriction or hypertonic saline injection in rats. Suppressed vCA1 neuronal activities under the hypertonic state were further confirmed with in vivo electrophysiological recording and the level of suppression paralleled both the duration and the total amount of water consumption. Chemogenetic inhibition of vCA1 pyramidal neurons increased water consumption in rats injected with both normal and hypertonic saline. These findings suggest that suppression of vCA1 pyramidal neuronal activities enhances water intake.

Pain-induced changes in motor unit discharge depend on recruitment threshold and contraction speed

At high forces, the discharge rates of lower and higher threshold motor units (MU) are influenced in a different way by muscle pain. These differential effects may be particularly important for performing contractions at different speeds since the proportion of lower and higher threshold MUs recruited varies with contraction velocity. We investigated whether MU discharge and recruitment strategies are differentially affected by pain depending on their recruitment threshold (RT), across a range of contraction speeds. Participants performed ankle dorsiflexion sinusoidal-isometric contractions at two frequencies (0.25Hz and 1Hz) and two modulation amplitudes [5% and 10% of the maximum voluntary contraction (MVC)] with a mean target torque of 20%MVC. High-density surface electromyography recordings from the tibialis anterior muscle were decomposed and the same MUs were tracked across painful (hypertonic saline injection) and non-painful conditions. Torque variability, mean discharge rate (MDR), DR variability (DRvar), RT and the delay between the cumulative spike train and the resultant torque output (neuromechanical delay, NMD) were assessed. The average RT was greater at faster contraction velocities (p=0.01) but was not affected by pain. At the fastest contraction speed, torque variability and DRvar were reduced (p<0.05) and MDR was maintained. Conversely, MDR decreased and DRvar and NMD increased significantly during pain at slow contraction speeds (p<0.05). These results show that reductions in contraction amplitude and increased recruitment of higher threshold MUs at fast contraction speeds appears to compensate for the inhibitory effect of nociceptive inputs on lower threshold MUs, allowing the exertion of fast submaximal contractions during pain.

The Efficacy of Ozone Prolotherapy Compared to Intra-Articular Hypertonic Saline Injection in Reducing Pain and Improving the Function of Patients with Knee Osteoarthritis: A Randomized Clinical Trial

Background. Knee osteoarthritis is a common disease that is associated with chronic pain and disability in patients. Prolotherapy is a complementary therapeutic approach for improving pain and function in patients with osteoarthritis. We aimed to compare the effect of hypertonic saline with ozone plus hypertonic saline in improving the symptoms of osteoarthritis in the patients. Materials and Method. In this clinical trial, thirty-four adults with painful primary knee osteoarthritis for at least three months were randomized to two groups: ozone plus hypertonic saline 5% and hypertonic saline 5% alone. Prolotherapy and thrice follow-up with two-week intervals were done. The outcome measures included Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analog Scale (VAS), which were obtained from the patients before the injection and after the 2nd and 4th weeks after the start of the study. Results. The mean age of the participants was 60.12 ± 7.54 years. There were no statistically significant differences between demographic characteristics before the injection between the two groups ( p > 0.05). The results showed that VAS and OKS values decreased over time ( p < 0.001) in each group, but there was no significant difference in the reduction of those between the two treatment groups ( p = 0.734 and p = 0.734, respectively). Both interventions improved the mean values of WOMAC pain, WOMAC stiffness, WOMAC act, and WOMAC total. However, there was no significant difference in WOMAC pain reduction rate ( p = 0.465), WOMAC stiffness rate ( p = 0.656), WOMAC act rate ( p = 0.376), and WOMAC total rate between the two methods ( p = 0.528). Conclusion. The results showed that intra-articular prolozone therapy and hypertonic saline injection can lead to improvement of pain and function in patients with knee osteoarthritis at the same status without any significant difference.

Experimental shoulder pain models do not validly replicate the clinical experience of shoulder pain

Background and aimsPeople with shoulder pain often present with abnormal shoulder muscle function. It is not known whether shoulder pain causes or is the result of muscle dysfunction. If pain leads to muscle dysfunction, therapeutic interventions that produce shoulder pain may be contraindicated. Experimentally induced nociception can be used to investigate a causal relationship between shoulder pain and muscle dysfunction. However, the validity of current experimental shoulder pain protocols has not been established. The aim of this study was to determine whether current experimental shoulder pain protocols validly replicate the clinical experience of shoulder pain with respect to pain distribution, quality and behaviour.MethodsNine pain free participants received two injections of hypertonic saline, one into the subacromial space and one into supraspinatus, in random order, at least 1 week apart. Investigators blind to the injection site assessed pain distribution, pain response to clinical tests which provoke shoulder pain and pain quality assessed using the McGill Pain Questionnaire.ResultsFollowing hypertonic saline injection into both the subacromial space and supraspinatus: pain was most commonly reported in the deltoid region and did not extend beyond the elbow; the most common response to clinical tests which provoke shoulder pain was a decrease in pain; and the highest rating of pain quality was in the sensory domain with very few responses in the affective domain.ConclusionsExperimental shoulder pain induced by injection of hypertonic saline into either the subacromial space or supraspinatus produced a pain distribution similar to that observed in clinical shoulder pain, but neither experimental pain protocol could reproduce the increases in pain intensity following shoulder provocation tests or the emotional distress commonly observed in people with clinical shoulder pain.ImplicationsPain induced by local shoulder nociception produced by hypertonic saline injection into shoulder structures has significant limitations as a model of clinical shoulder pain. While it is perhaps unsurprising that short duration, chemically-induced experimental pain does not replicate the quality of the clinical experience of shoulder pain, the validity of experimental shoulder pain models which produce the opposite response to provocation testing to clinical shoulder pain must be questioned.

Long-term Potentiation of Orofacial Sensorimotor Processing by Noxious Input from the Semispinal Neck Muscle in Mice

Tension-type headache is the most common type of primary headaches but no conclusive concept of pathophysiology exists. This may be due to a lack of an appropriate animal model. This study addressed the hypothesis that noxious neck muscle input induces central sensitization of orofacial sensorimotor processing. The effect of hypertonic saline injection into the semispinal neck muscle on the jaw-opening reflex (JOR) was investigated in anaesthetized mice ( n = 11). Hypertonic saline injection into the neck muscle facilitated the JOR for at least one hour: integral (+94.5%) and duration (+18.7%) increased, latency decreased (-7.5%). The reflex threshold decreased to 61% after injection. Isotonic saline injection into the neck muscle ( n = 11) or hypertonic saline injection into a hindpaw muscle ( n = 10) did neither change the reflex integral nor the threshold. Long-term potentiation of the JOR by noxious neck muscle input may be an appropriate model to investigate tension-type headache pathophysiology.

Increased heat-escape/cold-seeking behavior following hypertonic saline injection in rats

We examined the effect of hypertonic saline injection on heat-escape/cold-seeking behavior in desalivated rats. Rats were exposed to 40°C heat after normal (154 mM NaCl, control) or hypertonic saline (2,500 mM NaCl) injection (1 ml/100 g body wt). The rats received a 0°C air for 30 s when they entered a specific area in an experimental box. Core temperature (Tc) surpassed 40°C in both conditions when 0°C air was not available. Hypertonic saline injection produced a lower baseline Tcthan control [36.9 ± 0.2 and 37.9 ± 0.2°C (means ± SE), P < 0.05] and a greater number of 0°C air rewards during the 2-h heat with lower Tc at the end (48 ± 1 and 34 ± 2, 37.6 ± 0.1, and 37.3 ± 0.1°C in the control and hypertonic saline injection trial, respectively, P < 0.05, n = 6). However, Tc was similar (37.7 ± 0.2 and 37.6 ± 0.4°C in the control and hypertonic saline injection trial, n = 5) when 0°C air was automatically and intermittently (35 times) given during the heat. Rats augment heat-defense mechanisms in response to osmotic stress by lowering the baseline Tc and increasing heat-escape/cold-seeking behavior.