Biomedical subjects

Frank Porreca

Publications and source records attributed to Frank Porreca.

75 records · Page 5Linked to original sources

PubMed1994

Tetracaine attenuates irritancy without attenuating desensitization produced by intravesical resiniferatoxin in the rat.

The irritancy of initial application of capsaicin and related substances limits their therapeutic potential as novel analgesics. The purpose of the present study was to determine whether the irritant properties of the potent, capsaicin-like compound resiniferatoxin (RTX) would be attenuated by pretreatment with a local anesthetic and to determine whether the local anesthetic had significant effects on RTX-induced desensitization of sensory afferents. A model of visceral nociception in which irritants are instilled directly into the bladder (intravesical, i.ves.) of awake, freely moving rats was used. The nociceptive response, abdominal licking (grooming) was scored for 15 min; locomotor activity was scored concurrently. Tetracaine (0.125-1.0%) attenuated the increases in abdominal licking produced by RTX (3.0 nmol) in a dose- and time-dependent manner. At high doses, tetracaine also suppressed locomotor activity. Thirty minutes and 24 h later, the same dose of RTX was administered again to assess development of desensitization of bladder sensory afferents. Rats that had been pretreated with saline showed decreases in licking behavior from the first to subsequent injections of RTX, indicating the development of desensitization. Tetracaine-pretreated rats showed equivalent or significantly greater decreases in licking behavior, suggesting that local anesthetic pretreatment either did not alter or enhanced development of desensitization to RTX. In a second experiment, tetracaine (0.25 or 0.5%) produced similar effects against a high dose of RTX (3.0 nmol), but did not consistently alter excitatory or desensitizing effects of a low dose of RTX (0.1 nmol).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

PubMed1993

Behavioral characterization of the excitatory and desensitizing effects of intravesical capsaicin and resiniferatoxin in the rat.

This study characterized the excitatory (nociceptive) and desensitizing (antinociceptive) properties of the natural pungent substances, capsaicin (CAP) and resiniferatoxin (RTX) instilled in the bladder (intravesical, i.ves.) via an indwelling cannula in awake, freely moving rats. The incidence of 9 behaviors was scored for 10 min following i.ves. vehicle or RTX (1.0 nmol). Abdominal licking and head-turning occurred significantly more often in RTX-treated rats compared to vehicle controls, whereas head-grooming, locomotion, rearing and biting did not differ between the two groups. Little or no vocalization, defecation or hindlimb hyperextension was observed in either RTX- or vehicle-treated rats. A second injection of either vehicle or RTX administered to RTX-treated rats 60 min later did not significantly increase abdominal licking or head-turning compared to vehicle controls; this subsequent lack of excitation was taken as a measure of desensitization. In a separate experiment, the first injection of i.ves. RTX (0.1-3.0 nmol) increased licking in a dose-dependent manner; in contrast, the first injection of i.ves. CAP (0.1-3.0 mumol) significantly increased licking only at the intermediate dose tested, 1.0 mumol. With each subsequent injection of the same drug and dose at 30-min intervals, licking increased to a lesser extent, such that it was not significantly different from control after the fourth injection. Rats treated with i.ves. CAP or RTX also did not show increased licking when administered the opposite treatment 30 min later (RTX or CAP, respectively), indicating cross-desensitization; however, i.ves. administration of a third, higher dose of RTX reinstated licking behavior in these 'desensitized' rats. Subcutaneous administration of CAP (18-180 mg/kg) or RTX (18-180 micrograms/kg) dose-dependently attenuated the excitatory response to i.ves. CAP and RTX administered 2 days later. Whereas rats treated systemically with RTX also were desensitized to the excitatory effects of RTX instilled in the eye (evaluated in the eye-wipe assay), rats treated i.ves. with RTX and vehicle-treated rats showed a normal eye-wiping response. Finally, pretreatment with i.ves. ruthenium red, a cation channel blocker, antagonized the excitatory and desensitizing effects of i.ves. RTX. This study demonstrates that repeated application of both CAP and RTX into the bladder produces behavioral effects indicative of local sensory afferent desensitization. I.ves. CAP and RTX appear to produce their excitatory and desensitizing effects via a common mechanism, which is dependent on cation channel activation.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intravesical↗

PubMed1990

The rat paw formalin test: comparison of noxious agents.

A comparison was made of the spontaneous nociceptive behaviors elicited by s.c. injection into the rat hind paw of the following 8 irritants: acetic acid, carrageenan, formalin, kaolin, platelet-activating factor, mustard oil (given topically), serotonin, and yeast. Two distinct quantifiable behaviors indicative of pain were identified: flinching/shaking of the paw and hindquarters and licking/biting of the injected paw. These behaviors were prolonged and intense after formalin and acetic acid. Formalin-induced flinching was biphasic across time, a finding potentially useful for the study of both acute and tonic pain. Of the remaining test agents, only yeast caused significant spontaneous behavioral activity, which was of low intensity but long duration. Different time-courses for nociceptive behavior and development of edema were demonstrated for formalin, acetic acid and yeast. It is therefore unlikely that these endpoints are causally related. Overall, the present data strongly support the use of formalin as a noxious stimulus in tonic pain research.

Acetates↗