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MP29-09 ROLE OF SPINAL MICROGLIA IN COLON-TO-BLADDER NEURAL CROSSTALK IN A RAT MODEL OF COLITIS
THE JOURNAL OF UROLOGYâ
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
MP29-08 SMALL FIBER POLYNEUROPATHY e A BIG CLUE TO ETIOLOGY AND MANAGEMENT OF CHRONIC PELVIC PAIN (CPP) Annie Chen*, Charles E. Argoff, Elise De, Albany, NY INTRODUCTION AND OBJECTIVES: We report prevalence of small fiber polyneuropathy (SFPN) in patients with refractory CPP and concurrent pain diagnoses. Studies show that patients with CPP have an average 2.4 pain comorbidities such as irritable bowel syndrome (IBS), interstitial cystitis (IC), and fibromyalgia (FM) [5, 8, 12]. The lack of a common etiology complicates treatment options. SFPN is emerging as a major contributor to unexplained multi-symptom syndromes involving chronic widespread pain and is often present in patients with IBS and FM [1, 7]. SFPN diagnosis can be confirmed via skin biopsy: decreased epidermal nerve fiber density is demonstrated on immunofluorescence. The reported “minimum prevalence” of SFPN is 53/ 100,000 [11]. In our practice a significant proportion of refractory CPP patients had biopsies consistent with SFPN, a finding that has not been reported in the literature. We propose that SFPN is a unifying underlying treatable mechanism for pain in the refractory CPP patient. Objective: To demonstrate the prevalence of SFPN in patients with refractory CPP and/multiple pain syndromes by diagnostic skin biopsy. METHODS: We evaluated refractory CPP patients for SFPN: epidermal nerve fiber density in 3mm punch biopsies of the lower extremity was evaluated by immunofluorescence. The sensitivity and specificity of the test are 78-92% and 65-90%, respectively. RESULTS: 17 (61%) of 28 patients were positive for SFPN. Comorbid conditions were high in our population including migraine (39%), IBS (36%), endometriosis (21%), FM (32%), IC (14%), GERD (50%), vulvodynia (7%), lower back pain (32%), and other types of chronic pain syndrome (35%). Duration of pain was not different between the SFPN (+) and (-) groups (8.36 years SD¼9.92 versus 6.03 years SD¼3.14); p¼0.42 based on sample t-test for unequal variances. Number of prior visits for pain and age also did not differ (16.4 prior visits versus 15.2 and average age 43 versus 47 for SFPN (+) versus (-)). CONCLUSIONS: The prevalence of SFPN in specialty referral patients with refractory CPP is remarkably high versus published population data. Consideration of SFPN shifts the focus from a syndrome complex to a unifying treatable disorder. Making the diagnosis of SFPN may result in treatments not usually offered to CPP patients such IVIG or other immunomodulatory therapies [3]. Identifying SFPN should be a priority in this population. Source of Funding: None
MP29-09 ROLE OF SPINAL MICROGLIA IN COLON-TO-BLADDER NEURAL CROSSTALK IN A RAT MODEL OF COLITIS Tsuyoshi Majima*, Yasuhito Funahashi, Nagoya, Japan; Naoki Kawamorita, Sendai, Japan; Yoshihisa Matsukawa, Tokunori Yamamoto, Nagoya, Japan; Naoki Yoshimura, PIttsburgh, PA; Momokazu Gotoh, Nagoya, Japan INTRODUCTION AND OBJECTIVES: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by instilling 50% trinitrobenzene sulfonic acid into the distal colon in groups B and C; vehicle was administered in group A. Minocycline (200 mg/day), a microglial inhibitor, was continuously infused into the intrathecal space in group C; groups A and B were given the vehicle. On day 7: (1) an awake cystometrogram (CMG) was performed; (2) nociceptive licking and freezing behavior induced by intravesical instillation of resiniferatoxin was observed; (3) the distal colon was stained with hematoxylin-eosin (HE); (4) immunofluorescence staining for CD 11b, a microglial marker, was performed on the L6 spinal cord;
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(5) reverse transcription polymerase chain reaction for mRNA was performed on the L6 spinal cord; (6) the bladder was stained with toluidine blue. RESULTS: (1) CMG in group B showed significantly (p < 0.01) shorter intercontraction intervals (ICI) than in group A. Group C showed significantly (p < 0.01) longer ICI than group B. (2) There were no significant differences in licking events among the 3 groups. However, the number of freezing events was significantly (p < 0.01) greater in group B than in group A. Group C showed significantly (p < 0.05) fewer freezing events than group B. (3) HE staining showed substantial inflammation in the distal colon in groups B and C compared with that in group A. (4) The number of CD 11b-positive cells significantly differed among groups in the following order: group B > group C > group A. (5) The mRNA expressions of interleukin-1b, chemokine ligand 3, and brain-derived neurotrophic factor in the L6 spinal cord were significantly (p<0.05) increased in group B compared with those in group A. However, group C showed significantly (p<0.05) less mRNA expression of these molecules than group B. (6) Toluidine blue staining in group B showed significantly (p<0.01) more total and degranulated mast cells in the bladder than group A. Group C showed significantly (p<0.05) fewer total and degranulated mast cells in the bladder than group B. CONCLUSIONS: Spinal microglia probably play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitic rats. Source of DK088836
Funding:
DOD
W81XWH-12-1-0565;
NIH
MP29-10 ALTERATIONS IN THE URINARY FUNGAL MYCOBIOME IN PATIENTS WITH BLADDER PAIN AND URINARY URGENCY A. Lenore Ackerman*, Jennifer Anger, Jie Tang, Karyn Eilber, Jayoung Kim, Michael Freeman, David Underhill, Los Angeles, CA; MAPP Research Network, Washington, DC INTRODUCTION AND OBJECTIVES: To investigate the influence of host-microbe interactions on lower urinary tract symptoms, we characterized changes in urinary fungal communities (the “mycobiome”) associated with urinary urgency and bladder pain. While alterations in the urinary bacterial microbiome are found in interstitial cystitis/bladder pain syndrome (IC/PBS) and overactive bladder (OAB), urinary fungal populations have remained completely uncharacterized, despite recent evidence implicating fungi in association with flare in chronic pelvic pain syndromes. METHODS: Catheterized urine specimens were obtained from IC/PBS (n¼12), OAB (n¼17), and asymptomatic patients (n¼14). After centrifugation, DNA was extracted from the cellular pellet. Following deep sequencing of the ITS1 fungal ribosomal gene, fungal taxa were identified by comparison to multiple fungal sequence databases. Using validated questionnaire data [the Genitourinary Pain Index (GUPI), OAB Questionnaire (OABq) and O’Leary-Sant Indices (ICSI/ICPI)], subjects were separated into tertiles based on symptomatic scores. Fungal community representation for each tertile was then examined while blinding for diagnosis. RESULTS: Comparison of microbial communities between the subjects with the lowest and highest scores on the GUPI, OABq, and ICSI/ICPI revealed decreased fungal diversity for patients with more severe symptoms, regardless of symptom type. Individual symptoms were associated with distinctive species profiles, regardless of diagnosis (Figure). Patients with severe bladder pain exhibited altered Malassezia spp. composition, while fear of leakage was inversely correlated with detectable Wickerhamomyces spp. CONCLUSIONS: The urinary mycobiome is altered in lower urinary tract symptoms, with loss of diversity correlating positively with symptom severity. Specific fungal community patterns correlated
Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017
MP29-08 SMALL FIBER POLYNEUROPATHY e A BIG CLUE TO ETIOLOGY AND MANAGEMENT OF CHRONIC PELVIC PAIN (CPP) Annie Chen*, Charles E. Argoff, Elise De, Albany, NY INTRODUCTION AND OBJECTIVES: We report prevalence of small fiber polyneuropathy (SFPN) in patients with refractory CPP and concurrent pain diagnoses. Studies show that patients with CPP have an average 2.4 pain comorbidities such as irritable bowel syndrome (IBS), interstitial cystitis (IC), and fibromyalgia (FM) [5, 8, 12]. The lack of a common etiology complicates treatment options. SFPN is emerging as a major contributor to unexplained multi-symptom syndromes involving chronic widespread pain and is often present in patients with IBS and FM [1, 7]. SFPN diagnosis can be confirmed via skin biopsy: decreased epidermal nerve fiber density is demonstrated on immunofluorescence. The reported “minimum prevalence” of SFPN is 53/ 100,000 [11]. In our practice a significant proportion of refractory CPP patients had biopsies consistent with SFPN, a finding that has not been reported in the literature. We propose that SFPN is a unifying underlying treatable mechanism for pain in the refractory CPP patient. Objective: To demonstrate the prevalence of SFPN in patients with refractory CPP and/multiple pain syndromes by diagnostic skin biopsy. METHODS: We evaluated refractory CPP patients for SFPN: epidermal nerve fiber density in 3mm punch biopsies of the lower extremity was evaluated by immunofluorescence. The sensitivity and specificity of the test are 78-92% and 65-90%, respectively. RESULTS: 17 (61%) of 28 patients were positive for SFPN. Comorbid conditions were high in our population including migraine (39%), IBS (36%), endometriosis (21%), FM (32%), IC (14%), GERD (50%), vulvodynia (7%), lower back pain (32%), and other types of chronic pain syndrome (35%). Duration of pain was not different between the SFPN (+) and (-) groups (8.36 years SD¼9.92 versus 6.03 years SD¼3.14); p¼0.42 based on sample t-test for unequal variances. Number of prior visits for pain and age also did not differ (16.4 prior visits versus 15.2 and average age 43 versus 47 for SFPN (+) versus (-)). CONCLUSIONS: The prevalence of SFPN in specialty referral patients with refractory CPP is remarkably high versus published population data. Consideration of SFPN shifts the focus from a syndrome complex to a unifying treatable disorder. Making the diagnosis of SFPN may result in treatments not usually offered to CPP patients such IVIG or other immunomodulatory therapies [3]. Identifying SFPN should be a priority in this population. Source of Funding: None
MP29-09 ROLE OF SPINAL MICROGLIA IN COLON-TO-BLADDER NEURAL CROSSTALK IN A RAT MODEL OF COLITIS Tsuyoshi Majima*, Yasuhito Funahashi, Nagoya, Japan; Naoki Kawamorita, Sendai, Japan; Yoshihisa Matsukawa, Tokunori Yamamoto, Nagoya, Japan; Naoki Yoshimura, PIttsburgh, PA; Momokazu Gotoh, Nagoya, Japan INTRODUCTION AND OBJECTIVES: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by instilling 50% trinitrobenzene sulfonic acid into the distal colon in groups B and C; vehicle was administered in group A. Minocycline (200 mg/day), a microglial inhibitor, was continuously infused into the intrathecal space in group C; groups A and B were given the vehicle. On day 7: (1) an awake cystometrogram (CMG) was performed; (2) nociceptive licking and freezing behavior induced by intravesical instillation of resiniferatoxin was observed; (3) the distal colon was stained with hematoxylin-eosin (HE); (4) immunofluorescence staining for CD 11b, a microglial marker, was performed on the L6 spinal cord;
e383
(5) reverse transcription polymerase chain reaction for mRNA was performed on the L6 spinal cord; (6) the bladder was stained with toluidine blue. RESULTS: (1) CMG in group B showed significantly (p < 0.01) shorter intercontraction intervals (ICI) than in group A. Group C showed significantly (p < 0.01) longer ICI than group B. (2) There were no significant differences in licking events among the 3 groups. However, the number of freezing events was significantly (p < 0.01) greater in group B than in group A. Group C showed significantly (p < 0.05) fewer freezing events than group B. (3) HE staining showed substantial inflammation in the distal colon in groups B and C compared with that in group A. (4) The number of CD 11b-positive cells significantly differed among groups in the following order: group B > group C > group A. (5) The mRNA expressions of interleukin-1b, chemokine ligand 3, and brain-derived neurotrophic factor in the L6 spinal cord were significantly (p<0.05) increased in group B compared with those in group A. However, group C showed significantly (p<0.05) less mRNA expression of these molecules than group B. (6) Toluidine blue staining in group B showed significantly (p<0.01) more total and degranulated mast cells in the bladder than group A. Group C showed significantly (p<0.05) fewer total and degranulated mast cells in the bladder than group B. CONCLUSIONS: Spinal microglia probably play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitic rats. Source of DK088836
Funding:
DOD
W81XWH-12-1-0565;
NIH
MP29-10 ALTERATIONS IN THE URINARY FUNGAL MYCOBIOME IN PATIENTS WITH BLADDER PAIN AND URINARY URGENCY A. Lenore Ackerman*, Jennifer Anger, Jie Tang, Karyn Eilber, Jayoung Kim, Michael Freeman, David Underhill, Los Angeles, CA; MAPP Research Network, Washington, DC INTRODUCTION AND OBJECTIVES: To investigate the influence of host-microbe interactions on lower urinary tract symptoms, we characterized changes in urinary fungal communities (the “mycobiome”) associated with urinary urgency and bladder pain. While alterations in the urinary bacterial microbiome are found in interstitial cystitis/bladder pain syndrome (IC/PBS) and overactive bladder (OAB), urinary fungal populations have remained completely uncharacterized, despite recent evidence implicating fungi in association with flare in chronic pelvic pain syndromes. METHODS: Catheterized urine specimens were obtained from IC/PBS (n¼12), OAB (n¼17), and asymptomatic patients (n¼14). After centrifugation, DNA was extracted from the cellular pellet. Following deep sequencing of the ITS1 fungal ribosomal gene, fungal taxa were identified by comparison to multiple fungal sequence databases. Using validated questionnaire data [the Genitourinary Pain Index (GUPI), OAB Questionnaire (OABq) and O’Leary-Sant Indices (ICSI/ICPI)], subjects were separated into tertiles based on symptomatic scores. Fungal community representation for each tertile was then examined while blinding for diagnosis. RESULTS: Comparison of microbial communities between the subjects with the lowest and highest scores on the GUPI, OABq, and ICSI/ICPI revealed decreased fungal diversity for patients with more severe symptoms, regardless of symptom type. Individual symptoms were associated with distinctive species profiles, regardless of diagnosis (Figure). Patients with severe bladder pain exhibited altered Malassezia spp. composition, while fear of leakage was inversely correlated with detectable Wickerhamomyces spp. CONCLUSIONS: The urinary mycobiome is altered in lower urinary tract symptoms, with loss of diversity correlating positively with symptom severity. Specific fungal community patterns correlated