The impact of prenatal stress on basal nociception and evoked responses to tail-docking and inflammatory challenge in juvenile pigs.

The consequences of tail-docking (at 2-4 days) and prenatal stress (maternal social stress during the 2nd third of pregnancy) on baseline nociceptive thresholds and responses to acute inflammatory challenge were investigated in juvenile pigs in two studies. Nociceptive thresholds were assessed on the tail root and on the hind foot using noxious mechanical and cold stimulation before and after acute inflammatory challenge by intradermal injection of 30 µg capsaicin (study 1) or 3% carrageenan (study 2) into the tail root. Four groups of 8 (study 1, n=14-16 pigs/treatment) or 5 (study 2, n=6 pigs/treatment/sex) week-old pigs were exposed to the main factors: maternal stress and treatment (docked vs. intact tails). In study 1, tail docking did not significantly alter thresholds to noxious mechanical stimulation, whilst prenatally stressed pigs had significantly higher baseline thresholds to noxious mechanical stimulation on the tail root and on the hind foot than unstressed pigs, whether tail-docked or intact. Capsaicin injection induced localised mechanical allodynia around the tail root in all treatment groups, but had no effect on noxious plantar mechanical responses; however prenatally stressed offspring exhibited significantly attenuated response thresholds to capsaicin compared to controls. In study 2 tail docking did not alter thresholds to either mechanical or noxious cold stimulation. Baseline response durations to noxious cold stimulation of the tail root were significantly shorter in both sexes of prenatally stressed pigs, whilst male but not female prenatally stressed pigs exhibited significantly higher baseline thresholds to mechanical stimulation than controls, although results in female pigs tended towards significance. Carrageenan injection into the tail root induced localised mechanical and cold allodynia in all treatment groups, effects that were attenuated in prenatally stressed pigs. Collectively, these findings indicate that prenatal stress can induce long-term alterations in nociceptive responses, manifest as a reduced sensitivity to noxious mechanical and cold stimulation and evoked inflammatory allodynia. Neonatal tail-docking does not lead to long-term alterations in nociception in pigs.

Development of a mechanical stimulator and force measurement system for the assessment of nociceptive thresholds in pigs.

A mechanical stimulator and force measurement system was developed to quantify withdrawal thresholds to noxious mechanical stimulation of the foot in young pigs. The device and associated PC software have design and control features not previously used in other mechanical stimulators. The device, capable of delivering stimulus rates between 2 and 17 mm/s, maximum force 27 N, was validated in a cross-over study on 8 juvenile pigs (6-8 weeks of age) to check the repeatability and reliability of force threshold measurement and assess its ability to measure changes in force threshold following an inflammatory challenge. Threshold force measurements were obtained over several time periods before and after the pigs received a 0.25 ml subcutaneous injection of 3% carrageenan in 0.01 M phosphate buffered saline (PBS) or PBS in the hind foot. Consistent withdrawal thresholds were measured in injected (ipsilateral) and contralateral feet, 24 h and 30 min prior to injection (mean 8.4; 95% CI 7.1-9.7 N). Carrageenan injection, but not PBS injection, induced a significant decrease in withdrawal thresholds 90 min after injection (4.6+/-0.9 N) which remained reduced for 6h after injection. The testing system provided reliable and reproducible measurements of foot withdrawal thresholds to noxious mechanical force in young pigs (weight range 32-39 kg), and was capable of detecting and monitoring changes in threshold sensitivity following the induction of acute local inflammation in the foot. The system is suitable for studying nociceptive mechanisms in pigs.

Neutering affects urinary bladder function by different mechanisms in male and female dogs.

Acquired urinary incontinence is a significant, incurable problem, prevalent in neutered bitches but rarely seen in entire bitches or males. Decreased urethral closure pressure has been proposed as a causative factor for altered detrusor contractility in the neutered bitch. In post menopausal women, acquired urinary incontinence is associated with acquired urinary incontinence and changes in collagen deposition within the bladder wall. The aim of this study was to determine effects of neutering on smooth muscle in the canine urinary bladder. Tissue bath studies were used to assess contractile function and morphometric analysis to determine percentage of collagen in the bladder wall from male and female, neutered and entire canines. Maximal response to both carbachol and neurogenic stimulation was significantly lower in bladder strips from neutered animals of both sexes. Sensitivity to carbachol was also significantly reduced by neutering in both sexes. The percentage of collagen was significantly higher in the bladder wall from neutered vs. entire females, which were similar to that of both neutered and entire males. Neutering a canine decreases urinary bladder responsiveness to muscarinic stimulation in vitro, in both sexes, but only increases the percentage of collagen in the bladder wall in females. While increased percentage collagen may predispose bitches to acquired urinary incontinence, the sex difference in this parameter indicates that more than one mechanism underlies the changes in bladder responsiveness seen following neutering. This alternative effect of neutering may be in the muscarinic receptor effector pathway and act as a therapeutic target for acquired urinary incontinence treatment.