Convergence and cross talk in urogenital neural circuitries.

Despite common comorbidity of sexual and urinary dysfunctions, the interrelationships between the neural control of these functions are poorly understood. The medullary reticular formation (MRF) contributes to both mating/arousal functions and micturition, making it a good site to test circuitry interactions. Urethane-anesthetized adult Wistar rats were used to examine the impact of electrically stimulating different nerve targets [dorsal nerve of the penis (DNP) or clitoris (DNC); L6/S1 trunk] on responses of individual extracellularly recorded MRF neurons. The effect of bladder filling on MRF neurons was also examined, as was stimulation of DNP on bladder reflexes via cystometry. In total, 236 MRF neurons responded to neurostimulation: 102 to DNP stimulation (12 males), 64 to DNC stimulation (12 females), and 70 to L6/S1 trunk stimulation (12 males). Amplitude thresholds were significantly different at DNP (15.0 ± 0.6 µA), DNC (10.5 ± 0.7 µA), and L6/S1 trunk (54.2 ± 4.6 µA), whereas similar frequency responses were found (max responses near 30-40 Hz). In five males, filling/voiding cycles were lengthened with DNP stimulation (11.0 ± 0.9 µA), with a maximal effective frequency plateau beginning at 30 Hz. Bladder effects lasted ≈ 2 min after DNP stimulus offset. Many MRF neurons receiving DNP/DNC input responded to bladder filling (35.0% and 68.3%, respectively), either just before (43%) or simultaneously with (57%) the voiding reflex. Taken together, MRF-evoked responses with neurostimulation of multiple nerve targets along with different responses to bladder infusion have implications for the role of MRF in multiple aspects of urogenital functions.

Changes in response properties of rostral ventromedial medulla neurons during prolonged inflammation: modulation by neurokinin-1 receptors.

Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate pain transmission in conditions such as inflammation, and thereby contribute to hyperalgesia. Since blockade of NK-1 receptors in the RVM can attenuate hyperalgesia produced by prolonged inflammation, we examined the role of NK-1 receptors in changes of response properties of RVM neurons following four days of hind paw inflammation with complete Freund's adjuvant. Recordings were made from functionally identified ON, OFF and NEUTRAL cells in the RVM. Spontaneous activity and responses evoked by a series of mechanical (10, 15, 26, 60, 100, and 180 g) and heat (34-50 °C) stimuli applied to the inflamed and non-inflamed hind paws were determined before and at 15 and 60 min after injection of the NK-1-antagonist L-733,060 or vehicle into the RVM. Prolonged inflammation did not alter the proportions of functionally-identified ON, OFF and NEUTRAL cells. ON cells exhibited enhanced responses to mechanical (60-100g) and heat (48-50 °C) stimuli applied to the inflamed paw, which were attenuated by L-733,060 but not by vehicle. Inhibitory responses of OFF cells evoked by mechanical stimuli applied to the inflamed paw were also inhibited by L-733,060, but responses evoked by stimulation of the contralateral paw were increased. Heat-evoked responses of OFF cells were not altered by L-733,060. Also, neither L-733,060 nor vehicle altered spontaneous ongoing discharge rate of RVM neurons. These data indicate that NK-1 receptors modulate excitability of ON cells which contribute to both mechanical and heat hyperalgesia, whereas NK-1 modulation of OFF cells contributes to mechanical hyperalgesia during prolonged inflammation.

A new device to quantify tactile sensation in neuropathy.

OBJECTIVE: To devise a rapid, sensitive method to quantify tactile threshold of finger pads for early detection and staging of peripheral neuropathy and for use in clinical trials. METHODS: Subjects were 166 healthy controls and 103 patients with, or at risk for, peripheral neuropathy. Subjects were screened by questionnaire. The test device, the Bumps, is a checkerboard-like smooth surface with 12 squares; each square encloses 5 colored circles. The subject explores the circles of each square with the index finger pad to locate the one circle containing a small bump. Bumps in different squares have different heights. Detection threshold is defined as the smallest bump height detected. In some subjects, a 3-mm skin biopsy from the tested finger pad was taken to compare density of Meissner corpuscles (MCs) to bump detection thresholds. RESULTS: The mean (±SEM) bump detection threshold for control subjects was 3.3 ± 0.10 µm. Threshold and test time were age related, older subjects having slightly higher thresholds and using more time. Mean detection threshold of patients with neuropathy (6.2 ± 0.35 µm) differed from controls (p < 0.001). A proposed threshold for identifying impaired sensation had a sensitivity of 71% and specificity of 74%. Detection threshold was higher when MC density was decreased. CONCLUSIONS: These preliminary studies suggest that the Bumps test is a rapid, sensitive, inexpensive method to quantify tactile sensation of finger pads. It has potential for early diagnosis of tactile deficiency in subjects suspected of having neuropathy, for staging degree of tactile deficit, and for monitoring change over time.