The afferent innervation of the lower urinary tract (LUT) arises in the lumbosacral dorsal root ganglia (DRG) and is carried in three sets of nerves: (1) pelvic and (2) hypogastric nerves which innervate the urinary bladder and urethra and (3) pudendal nerves which innervate the mid-distal urethra and urethral sphincter. These afferent pathways exhibit a wide range of properties. Bladder mechano-sensitive afferents in the pelvic nerves have small myelinated (A-δ fibre) and unmyelinated axons (C-fibre) which respond to slow bladder filling and provide information about bladder wall tension and bladder volume. On the other hand, mechano-insensitive C-fibre afferents respond to chemical and/or nociceptive stimuli. Afferent input from the LUT to the spinal cord has an essential role in the initiation of urine storage and voiding reflexes as well as painful sensations. Low levels of afferent activity induced by bladder distension trigger reflex contractions of the urethral outlet and promote continence, whereas high levels of activity induce reflex bladder contractions and voiding. Bladder afferent neurons synthesize several putative neurotransmitters including neuropeptides, glutamate acid and nitric oxide. These neurons also express various types of receptors including transient receptor potential (TRP), purinergic, neurokinin and neurotrophic factor (NTF) receptors. Recordings from bladder afferent neurons or afferent nerves showed that activation of these receptors enhances excitability. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways leading to urinary urgency, urinary incontinence and pain. Electrophysiological studies conducted on bladder sensory neurons from cats and rats identified several mechanisms that contribute to acute and chronic afferent sensitization. A-δ bladder dorsal root ganglion (DRG) cells are generally resistant to capsaicin and have tetrodotoxin-sensitive (TTX-S) Na+ channels and action potentials (APs); whereas C-fibre bladder DRG cells are capsaicin sensitive, have TTX-resistant (TTX-R) Na+ channels and APs and have a low threshold A-type K+ current (IA) that controls the firing threshold of the cells (1, 2). A-δ DRG cells fire trains of APs (tonic activity) in response to a prolonged depolarizing current pulse; whereas C-fibre DRG cells fire one or two APs (phasic activity) to this stimulus (3). Chronic spinal cord injury (SCI) in rats increases TTX-S Na+ currents in C-fibre bladder DRG cells (2). SCI in cats and rats or chemical cystitis (CC) in rats also reduces IA, reduces the threshold for firing and induces tonic activity in C-fibre DRG neurons (3, 4). CC increases the expression of P2X purinergic receptors in bladder DRG cells and enhances the excitatory effect of ATP on bladder afferent nerves (5). Bladder inflammation increases the expression of nerve growth factor (NGF) in the bladder raising the possibility that NGF contributes to the change in afferent properties (4). This was confirmed by administering NGF chronically to the bladder or the spinal cord (6). Following this treatment the bladder was hyperactive and bladder DRG neurons exhibited changes in IA and firing similar to those induced by SCI or CC. Acute treatment of capsaicin-sensitive C-fibre DRG neurons with agents (4-aminopyridine or substance P) that suppress K+ channels also converts phasic firing to tonic firing. Patch clamp recordings in capsaicin-sensitive DRG neurons from cats with feline interstitial cystitis (FIC), a chronic naturally occurring painful bladder condition, have revealed changes in IA and firing similar to those described in rats with CC or treated with NGF. In addition, the currents induced by capsaicin were increased in amplitude and exhibited a slower desensitization. These findings suggest that the bladder symptoms in FIC cats are related to changes in K+ and TRPVl channels in sensory neurons. Recent studies have revealed that the urothelium has specialized sensory and signaling properties that allows urothelial cells to respond to their chemical and physical environment and to engage in chemical communication with neighboring afferent nerves (7). The role of ATP in urothelial-afferent communication has attracted considerable attention because ATP excites sensory nerves and bladder distension releases ATP from the urothelium. In FIC cats and patients with interstitial cystitis ATP release from urothelial cells is significantly increased above normal levels, raising the possibility that enhanced signaling between the urothelium and afferent nerves contributes to painful bladder sensations. In summary, alterations in the expression and/or properties of ion channels (Na+, K+ and TRPVl) and altered chemical communication between the urothelium and afferent nerves could contribute to abnormal sensory mechanisms in the bladder in pathological conditions.