Limits...
Optimization of a pain model: effects of body temperature and anesthesia on bladder nociception in mice.

Sadler KE, Stratton JM, DeBerry JJ, Kolber BJ - PLoS ONE (2013)

Bottom Line: Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used.These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD.For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5°C and isoflurane induction should gradually decrease over the course of 90 minutes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urological condition that is resistant to treatment and poorly understood. To determine novel molecular treatment targets and to elucidate the contribution of the nervous system to IC/BPS, many rodent bladder pain models have been developed. In this study we evaluated the effects of anesthesia induction and temperature variation in a mouse model of bladder pain known as urinary bladder distension (UBD). In this model compressed air is used to distend the bladder to distinct pressures while electrodes record the reflexive visceromotor response (VMR) from the overlying abdominal muscle. Two isoflurane induction models are commonly used before UBD: a short method lasting approximately 30 minutes and a long method lasting approximately 90 minutes. Animals were anesthetized with one of the methods then put through three sets of graded bladder distensions. Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used. In order to determine the effect of temperature on VMRs, animals were put through three graded distension sets at 37.5 (normal mouse body temperature), 35.5, and 33.5°C. Distensions performed at 33.5 and 35.5°C were significantly lower than those performed at 37.5°C. Additionally, Western blot analysis revealed significantly smaller increases in spinal levels of phosphorylated extracellular-signal regulated kinase 2 (pERK2) following bladder distension in animals whose body temperature was maintained at 33.5°C as opposed to 37.5°C. These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD. For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5°C and isoflurane induction should gradually decrease over the course of 90 minutes.

Show MeSH

Related in: MedlinePlus

Visceromotor responses (VMR) from urinary bladder distension (UBD).(A) Schematic of UBD setup. Compressed air is delivered into bladder via urethral catheter. During distensions, electrodes in abdominal muscle record EMG. Temperature is maintained throughout the procedure using a battery operated heating pad and overhead lamp. (B) Example EMG traces during UBD. As pressure increases, electrical output from abdominal muscles increases congruently. (C) Example VMR from one complete set of distensions. During each set, the bladder is distended three times at each pressure. VMRs are normalized with 20 s pre-distension interval then averaged for each pressure.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3818235&req=5

pone-0079617-g001: Visceromotor responses (VMR) from urinary bladder distension (UBD).(A) Schematic of UBD setup. Compressed air is delivered into bladder via urethral catheter. During distensions, electrodes in abdominal muscle record EMG. Temperature is maintained throughout the procedure using a battery operated heating pad and overhead lamp. (B) Example EMG traces during UBD. As pressure increases, electrical output from abdominal muscles increases congruently. (C) Example VMR from one complete set of distensions. During each set, the bladder is distended three times at each pressure. VMRs are normalized with 20 s pre-distension interval then averaged for each pressure.

Mentions: Approximately 3–8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination as well as nocturia and general pelvic pain [1]. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients [2]. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. Traditionally, inflammatory agents such as cyclophosphamide [3], hydrochloric acid [4], acetone [5], mustard oil [6], lipopolysaccharide [7], [8], and infection with E.coli[8] have been used to induce sensitization of the bladder to model IC/BPS. However, since the exact inflammatory conditions accompanying IC/BPS are unknown, the non-specific bladder inflammation and contaminated urine in these models fails to mimic the real symptoms associated with the disease. An alternative or addition to these models is urinary bladder distension (UBD)[9]. In UBD, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure wires in the superior oblique abdominal muscles record electrical activity known as the visceromotor response (VMR) (Figure 1). This activity is a reliable, reproducible measure of nociception [9]. To maintain VMR consistency between animals, confounding variables such as method of anesthesia induction and body temperature need to be taken into consideration. However, to date no study has systematically looked at the effects of these two factors on VMRs.


Optimization of a pain model: effects of body temperature and anesthesia on bladder nociception in mice.

Sadler KE, Stratton JM, DeBerry JJ, Kolber BJ - PLoS ONE (2013)

Visceromotor responses (VMR) from urinary bladder distension (UBD).(A) Schematic of UBD setup. Compressed air is delivered into bladder via urethral catheter. During distensions, electrodes in abdominal muscle record EMG. Temperature is maintained throughout the procedure using a battery operated heating pad and overhead lamp. (B) Example EMG traces during UBD. As pressure increases, electrical output from abdominal muscles increases congruently. (C) Example VMR from one complete set of distensions. During each set, the bladder is distended three times at each pressure. VMRs are normalized with 20 s pre-distension interval then averaged for each pressure.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818235&req=5

pone-0079617-g001: Visceromotor responses (VMR) from urinary bladder distension (UBD).(A) Schematic of UBD setup. Compressed air is delivered into bladder via urethral catheter. During distensions, electrodes in abdominal muscle record EMG. Temperature is maintained throughout the procedure using a battery operated heating pad and overhead lamp. (B) Example EMG traces during UBD. As pressure increases, electrical output from abdominal muscles increases congruently. (C) Example VMR from one complete set of distensions. During each set, the bladder is distended three times at each pressure. VMRs are normalized with 20 s pre-distension interval then averaged for each pressure.
Mentions: Approximately 3–8 million people in the United States suffer from interstitial cystitis/bladder pain syndrome (IC/BPS), a debilitating condition characterized by increased urgency and frequency of urination as well as nocturia and general pelvic pain [1]. Despite years of research, the cause of IC/BPS remains elusive and treatment strategies are unable to provide complete relief to patients [2]. In order to study nervous system contributions to the condition, many animal models have been developed to mimic the pain and symptoms associated with IC/BPS. Traditionally, inflammatory agents such as cyclophosphamide [3], hydrochloric acid [4], acetone [5], mustard oil [6], lipopolysaccharide [7], [8], and infection with E.coli[8] have been used to induce sensitization of the bladder to model IC/BPS. However, since the exact inflammatory conditions accompanying IC/BPS are unknown, the non-specific bladder inflammation and contaminated urine in these models fails to mimic the real symptoms associated with the disease. An alternative or addition to these models is urinary bladder distension (UBD)[9]. In UBD, compressed air of a specific pressure is delivered to the bladder of a lightly anesthetized animal over a set period of time. Throughout the procedure wires in the superior oblique abdominal muscles record electrical activity known as the visceromotor response (VMR) (Figure 1). This activity is a reliable, reproducible measure of nociception [9]. To maintain VMR consistency between animals, confounding variables such as method of anesthesia induction and body temperature need to be taken into consideration. However, to date no study has systematically looked at the effects of these two factors on VMRs.

Bottom Line: Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used.These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD.For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5°C and isoflurane induction should gradually decrease over the course of 90 minutes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences and Chronic Pain Research Consortium, Duquesne University, Pittsburgh, Pennsylvania, United States of America.

ABSTRACT
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urological condition that is resistant to treatment and poorly understood. To determine novel molecular treatment targets and to elucidate the contribution of the nervous system to IC/BPS, many rodent bladder pain models have been developed. In this study we evaluated the effects of anesthesia induction and temperature variation in a mouse model of bladder pain known as urinary bladder distension (UBD). In this model compressed air is used to distend the bladder to distinct pressures while electrodes record the reflexive visceromotor response (VMR) from the overlying abdominal muscle. Two isoflurane induction models are commonly used before UBD: a short method lasting approximately 30 minutes and a long method lasting approximately 90 minutes. Animals were anesthetized with one of the methods then put through three sets of graded bladder distensions. Distensions performed following the short anesthesia protocol were significantly different from one another despite identical testing parameters; this same effect was not observed when the long anesthesia protocol was used. In order to determine the effect of temperature on VMRs, animals were put through three graded distension sets at 37.5 (normal mouse body temperature), 35.5, and 33.5°C. Distensions performed at 33.5 and 35.5°C were significantly lower than those performed at 37.5°C. Additionally, Western blot analysis revealed significantly smaller increases in spinal levels of phosphorylated extracellular-signal regulated kinase 2 (pERK2) following bladder distension in animals whose body temperature was maintained at 33.5°C as opposed to 37.5°C. These results highlight the significance of the dynamic effects of anesthesia on pain-like changes and the importance of close monitoring of temperature while performing UBD. For successful interpretation of VMRs and translation to human disease, body temperature should be maintained at 37.5°C and isoflurane induction should gradually decrease over the course of 90 minutes.

Show MeSH
Related in: MedlinePlus