Urothelium has been a new key for vesical pain and/or the unusual sensation form the urinary bladder. Afferent fibers in the smooth muscle are mostly A delta fibers and sensitive to distention of the urinary bladder, In contrast, C-fibers in the pelvic afferent fibers were called as “silent fibers”, since the functional significance during the normal micturition was not clear. Recent histological study demonstrated unmyelinated fibers were located submucosal area and urothelium. These contained CGRP and/or substance P. TRPV1 channel in the urothelium released ATP, and P2X3 receptors in the afferent nerve terminals elicited the neural activities. Alpha-1D receptors were also in the urothelium and released ATP. Acetylcholine receptors (M2 and M3 and nicotinic receptors) presented in the urothelium. Acetylcholine was also released from the urothelium. During the inflammation of the urinary bladder, prostaglandin E2 in the urine was increased. EP1 receptors, prostaglandin receptors, presented in the urothelium and primary afferent nerve terminals. These also increased the afferent activity. Variety of neurotransmitter receptors and channels in the urothelium releasing ATP and acetylcholine should be important for controlling the micturition reflex in the pathological condition including the visceral pain.

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   The actigraph has been widely used for the assessment of activity patterns, such as insomniac sleep. The reliability of the actigraph has been well proven. Measurement of with the actigraph may make it possible to objectively assess the activity of patients with pain as well as insomnia. The purpose of the present study was to determine the usefulness of the wrist actigraph for the study of the effect of morphine on the activity of patients with cancer pain. Single rescue morphine (1.5 or 3.0 mg) was administered subcutaneously to two patients with continuous morphine injection (37.5 or 67.5 mg/day, respectively). We compared the patient's activity with morphine concentrations in the blood and with pain intensity measured with visual analog scale (VAS). Single rescue morphine significantly decreased activity scores from 15 to 45 minutes after injection in both cases. The average of activity scores after 16 rescue injections (1.5 mg morphine) revealed the significant decrease of the activity from 15 to 180 minutes after injection in case 1. Single rescue injections of morphine significantly decreased VAS scores from 15 to 120 minutes after injection.

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   The purpose of this study was to determine whether D-serine, an endogenous N-methyl-D-aspartate (NMDA) receptor agonist, enhances nociception at the spinal level, as compared with the nociceptive effect of glycine. The following drugs were injected intrathecally through a previously implanted polyethylene tube in rats: 10 µl of physiological saline as control; 2 pmol, 2 µmol, or 2 mmol of D-serine or L-serine; 10 µmol of glycine; and 5 pmol of strychnine. Formalin (0.625% and 1.25%, 50 µl) was injected subcutaneously into the left hind paw 15 min after each agent. The number of flinches was counted as nociceptive behavior in the early phase (0 - 10 min), first late phase (11 - 30 min), and second late phase (31 - 60 min) after injection of formalin. Flinching occurred only during the early stage after the injection of 0.625% formalin. All doses of D-serine, however, significantly restored late stages of the flinching response after injection of 0.625% formalin. In rats given an injection of 1.25% formalin, the lowest and middle dose levels of D-serine significantly potentiated both first and second late stages of the flinching response. Treatment with L-serine had no significant effect on the flinching responses induced by 0.625% or 1.25% formalin. In contrast, injection of 10 µmol glycine significantly decreased the total number of flinches during the late phase, and this response was antagonized by treatment with 5 pmol strychnine. Our results indicate that D-serine in the spinal cord is closely involved in the modulation of inflammatory pain and that its role in nociception differs from that of glycine.

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