Francisco Cruz | Vignan University (original) (raw)

Papers by Francisco Cruz

Pain, 1996

Activation of the protooncogene c-fos at spinal cord segments T12-L2 and L5-S1 was used to study ... more Activation of the protooncogene c-fos at spinal cord segments T12-L2 and L5-S1 was used to study the effects of topical administration of capsaicin on bladder primary afferents coursing in the hypogastric (HGN) or pelvic (PN) nerves of adult rats. Two hours after capsaicin instillation in the bladder numerous Fos cells occurred in lamina I at T12-L2 and in lamina 1, intermediolateral gray matter (ILG) and dorsal commissure (DCM) at L5-S1. Twenty-four hours later, the Fos immunoreaction had disappeared from the spinal cord. At this time, instillation of 1% acetic acid into the bladder of capsaicin-treated rats induced considerably fewer Fos cells than in animals that had been instilled only with the vehicle solution for capsaicin. The difference in the average number of Fos cells was statistically significant in lamina I, ILG and DCM at L5-S1 but not in lamina I at T12-L2. Thus, intravesical capsaicin at the doses used excites bladder primary afferents coursing in the HGN and PN, but only desensitizes those coursing in the PN. It is suggested that this may depend on the differential occurrence of capsaicin receptors in the two nerves.

European Urology, 2000

Recent experimental studies have identified a category of unmyelinated type C bladder afferent fi... more Recent experimental studies have identified a category of unmyelinated type C bladder afferent fibers in the pelvic nerves which are extremely sensitive to capsaicin. Sensory input conveyed by these fibers triggers a spinal reflex which, in chronic spinalized animals, facilitates and controls micturition. In addition, bladder C fibers were also shown to have a role in bladder pain perception. In humans capsaicin-sensitive afferent fibers also innervate the bladder and contribute to the reflexogenic control of the detrusor muscle and to bladder pain perception. Desensitization of such fibers by intravesical administration of capsaicin, presumably by blocking sensory transmission, has been shown to reduce involuntary micturition and to increase bladder capacity in patients with detrusor hyperreflexia of spinal origin, and to reduce the intensity of bladder pain in patients with bladder hypersensitivity. Very recently, resiniferatoxin, an ultrapotent capsaicin analog, was shown to have a similar clinical effect in this subset of patients. However, unlike capsaicin, resiniferatoxin did not evoke acute irritative urinary symptoms during bladder instillation.

European Journal of Pharmacology, 1999

In this study the desensitizing power of increasing concentrations of resiniferatoxin applied top... more In this study the desensitizing power of increasing concentrations of resiniferatoxin applied topically to the bladder mucosa, and the irritating properties of the most effective desensitizing dose, were determined with the aid of the spinal expression of the proto-oncogene c-fos. Desensitization was assessed by the decrease in the number of Fos-immunoreactive spinal neurons induced by the intravesical instillation of 1% acetic acid, when the latter was preceded by resiniferatoxin in concentrations between 1 and 1000 nM. Irritation, as shown by the noxious excitation of vesical sensory innervation, was measured by the c-fos response evoked by a single application of resiniferatoxin. As to the desensitizing power, resiniferatoxin produced a dose-dependent effect with a maximum at 100 nM, which decreased Fos-immunoreactive cell numbers to less than 10% of controls. No further decrease of c-fos activation occurred at 1000 nM. As to the irritating power, the saturation dose of resiniferatoxin (100 nM) produced a very weak c-fos activation in lumbosacral spinal cord segments. These data show that in an effective desensitizing concentration, resiniferatoxin is virtually devoid of nociceptive effects, in agreement with current clinical observations.

Obstetrical & Gynecological Survey, 1993

Several recent reports have indicated an increased prevalence of gallstones in association with p... more Several recent reports have indicated an increased prevalence of gallstones in association with pregnancy. If these reports are true, the early puerperium should be a favorable time to detect the disease in its initial stages and follow its natural course. Accordingly, the gallbladder was examined by ultrasound in 980 women during the immediate postpartum period and in 150 nulliparous, age-matched healthy volunteers. Gallstones were detected in 12.2% of the puerperal women and in 1.3% of the control group. In 70 patients who had stones in a functioning gallbladder, 22 (31%) had had attacks of biliary colic. The history of pain was more common in patients with stones greater than 10 mm in diameter. Forty-one women with small stones (< 10 mm) were followed clinically and ultrasonographically for between 6 and 24 (mean = 8.7) mo. All remained pain-free, and in twelve subjects (29%) the stones disappeared. Gallbladder bile was examined in 11 normal volunteers (controls) immediately after delivery and in 19 women with small stones 39 +/- 6 days postpartum. Bile was saturated with cholesterol in the controls and was unsaturated in patients with gallstones. We conclude that in our population pregnancy is a very important pathogenetic factor favoring gallstone formation. Attacks of biliary colic appear early and frequently in young Chilean women with this disease. Unexplained disappearance of small stones frequently occurs: in some cases it is likely to be the result of spontaneous dissolution because bile becomes unsaturated within a few weeks of delivery.

Trends in Molecular Medicine, 2006

The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli rangi... more The vanilloid receptor TRPV1 is now recognized as a molecular integrator of painful stimuli ranging from noxious heat to endovanilloids in inflammation. Pharmacological blockade of TRPV1 represents a new strategy in pain relief. TRPV1 antagonists are expected to prevent pain by silencing receptors where pain is generated rather than stopping the propagation of pain, as most-traditional pain killers do. This hypothesis has already being tested in the clinic by administering small molecule TRPV1 antagonists (e.g. GlaxoSmithKline SB-705498) for migraine and dental pain. Paradoxically, in some murine models of chronic pain, TRPV1-deficient mice exhibit more pain-related behavior than their wildtype littermates, indicating that the understanding of TRPV1 in pain is still incomplete. Moreover, there is mounting evidence to suggest the existence of functional TRPV1 both in the brain and in various non-neuronal tissues. The biological role of these receptors remains elusive, but their tissue distribution clearly indicates that they are involved in many more functions than just pain perception. Here, we review the potential therapeutic indications and adverse effects of TRPV1 antagonists.

The Journal of …, 2004

The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia... more The role of anandamide in the development of inflammatory hyperalgesia and visceral hyperreflexia was studied in the rat urinary bladder. Animals were given intraperitoneal cyclophosphamide injection, which evokes painful hemorrhagic cystitis accompanied by increased bladder reflex activity. The vanilloid receptor 1 [transient receptor potential vanilloid 1 (TRPV1)] antagonist capsazepine, applied onto the serosal surface of bladders, significantly reduced the hyperreflexia. Mass spectrometric analysis revealed that cyclophosphamide injection significantly and persistently increased the anandamide content of bladder tissues. The increase in the anandamide content paralleled the development of reflex hyperactivity. Anandamide (1-100 microm), applied onto the serosal surface of naive bladders, increased the reflex activity in a concentration-dependent manner. Repeated anandamide applications did not produce desensitization of the response. The anandamide-evoked effect was blocked by capsazepine or by instillation of resiniferatoxin, the ultrapotent TRPV1 agonist, into the bladders 24 hr before the anandamide challenge. The cannabinoid 1 receptor antagonist SR141716A [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] significantly increased the potency of anandamide in enhancing bladder reflex activity in naive but not in cyclophosphamide-injected animals. Application of the fatty acid amide hydrolyze inhibitor palmitoylisopropylamine onto the serosal surface of bladders also increased the reflex activity both in naive and cyclophosphamide-injected rats. This latter effect in naive animals was blocked by capsazepine and by resiniferatoxin pretreatment. Finally, intravesical instillation of anandamide (50 microm) increased c-fos expression in the spinal cord, which was reduced by capsazepine or by resiniferatoxin pretreatment. These results suggest that anandamide, through activating TRPV1, contributes to the development of hyperreflexia and hyperalgesia during cystitis.

Journal of Urology, 1997

Purpose: Capsaicin was used to treat symptomatic patients with hyperactive or hypersensitive blad... more Purpose: Capsaicin was used to treat symptomatic patients with hyperactive or hypersensitive bladders.

Journal of Urology, 2002

Purpose: We evaluated the role of bladder C-fiber input in involuntary detrusor activity in patie... more Purpose: We evaluated the role of bladder C-fiber input in involuntary detrusor activity in patients with idiopathic detrusor instability.