Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture.

Abstract

Isocapnic dry gas hyperventilation provokes hyperpnea-induced bronchoconstriction in guinea pigs by releasing tachykinins from airway sensory C-fiber neurons. It is unknown whether dry gas hyperpnea directly stimulates Cfibers to release tachykinins, or whether this physical stimulus initiates a mediator cascade that indirectly stimulates C-fiber tachykinin release. We tested the hypotheses that mucosal hypothermia and/or hyperosmolarity-physical consequences of airway heat and water loss imposed by dry gas hyperpnea-can directly stimulate C-fiber tachykinin release. Neurons isolated from neonatal rat dorsal root ganglia were maintained in primary culture for 1 wk. Cells were then exposed for 30 min at 370C to graded concentrations of NaCl, mannitol, sucrose, or glycerol (0-600 mOsm) added to isotonic medium, or to isotonic medium at 250C without or with 462 mOsm mannitol added. Fractional release of substance P (SP) was calculated from supernatant and intracellular SP contents following exposure. Hyperosmolar solutions containing excess NaCl, mannitol, or sucrose all increased fractional SP release equivalently, in an osmolarity-dependent fashion. In marked contrast, hypothermia had no effect on fractional SP release under isotonic or hypertonic conditions. Thus, hyperosmolarity, but not hypothermia, can directly stimulate tachykinin release from cultured rat sensory C-fibers. The lack of effect of glycerol, a solute which quickly crosses cell membranes, suggests that neuronal volume change represents the physical stimulus transduced by C-fibers during hyperosmolar exposure. (J. Clin. Invest. 1995Invest. . 95:2359Invest. -2366

A Novel Experimental Knee-Pain Model Affects Perceived Pain and Movement Biomechanics

“…Also, results 49,50 from animal experiments suggest that group III and IV nociceptive afferents are active due to hypertonic saline, providing more evidence that the pathways involved in EKP are similar to musculoskeletal pain. Researchers 48 have also reported that hypertonic saline induces the release of substance P from C-fiber neurons, which is consistent with musculoskeletal pain. We assume that C-fiber sensory information is responsible for the biomechanical alterations we observed.…”

“…Although the perceived pain levels appeared to be sufficient (Figure 2), whether other characteristics of this EKP pain are representative is unknown. Previous authors [47][48][49][50] supported the idea that EKP induced by hypertonic saline is representative of joint pain related to knee injury. Investigators 47 have reported that the nature, quality, and distribution of pain elicited by hypertonic saline is similar to clinical anterior knee joint pain.…”

Activation of heat-shock transcription factor 1 by hypertonic shock in 3T3 cells

“…This suggests that the increased and persistent osmotic pressure on the extracellular side of the plasma membrane, rather than the osmotic strength per se, acts as a trigger for HSF activation. Interestingly, neuronal volume has been found to be altered more by exposure to hyperosmolar conditions resulting from impermeable or poorly permeable osmolytes than to those resulting from glycerol [32]. However, it should be borne in mind that glycerol, in common with other polyols, may well protect proteins from denaturation [33].…”

The angiotensin II receptors type 1 blockage affects the urinary bladder activity in hyperosmolar-induced detrusor overactivity in rats: Preliminary results

“…High concentrated urine penetrates the submucosal layers of the urinary bladder and activates capsaicin-sensitive C neurons and consequently, inducing neurogenic inflammation, which leads to DO. 7 The water deprivation for 16 h is sufficient to determine urine concentrating ability of kidneys. The urine concentration tests in female rats revealed that mean urine osmolarity was 2080 mOsm/L.…”