Mechanism of Hyperalgesia in SART Stressed (Repeated Cold Stress) Mice: Antinociceptive Effect of Neurotropin

Abstract

Exposing mice to 24 and 4°C in alternate 1 hr periods in the day time and maintaining 4°C at night for several days decreases the tail clamp pressure re quired to evoke pain behavior. This model is referred to as SART (specific alterna tion rhythm of temperature) stress. An extract from inflamed skin of rabbits inocu lated with vaccinia virus (neurotropin) clearly normalized the hyperalgesia in this SART stress model. To clarify the mechanism of the hyperalgesia in SART mice and the mode of the antinociceptive action of neurotropin in this model, the influence of systemically administered neurotransmitter related drugs was studied. 1) Neurotropin, 5-hydroxytryptophan and L-dihydroxyphenylalanine significantly normalized the de crease in nociceptive threshold, and muscimol tended to inhibit it in nociceptive threshold in SART stressed mice. 2) Haloperidol, phenoxybenzamine, reserpine, bicu culline, scopolamine, physostigmine and naloxone alone did not influence the nocicep tive threshold in SART stressed mice.3) The antinociceptive effect of neurotropin was significantly attenuated by p-chlorophenylalanine, haloperidol and phenoxybenza mine; and it was completely inhibited by reserpine. 4) Naloxone, bicuculline, scopola mine and physostigmine had no influence on the antinociceptive effect of neurotropin. These results suggest that hypofunction mainly of the monoaminergic systems contrib utes to hyperalgesia in SART stressed mice and that neurotropin produces the anti nociceptive effect by restoring these neural functions.

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…The role of monoamines in negative affective state is well described. Systemic administration of 5-Hydroxytryptophan, a precursor of 5-HT, and L-DOPA, a precursor of dopamine, abolished repeated cold stress-induced hyperalgesia in mice (Ohara et al, 1991).…”

Evaluation of the alleviative action of neurotropin for penile pain associated with intracavernous injection of prostaglandin E1 assessed using the visual analogue scale

“…9 Neurotropin has an anti-nociceptive action, which might be induced through the modulation of monoaminergic and GABAergic system functions. 10,16 These effects also might contribute to alleviation of penile pain.…”

Animal Models of Fibromyalgia

“…The repeated cold stress model was first introduced as an animal model to study autonomic imbalance in response to sudden changes in environmental temperature (Kita et al, 1975;Ohara et al, 1991). Mice exposed to repeated cold stress develop several abnormal physiologies such as a continuous lowering of blood pressure, sympathicotonic-type electrocardiogram (ECG), depression-like behaviors, and hyperalgesia (Ohara et al, 1991).…”

“…Mice exposed to repeated cold stress develop several abnormal physiologies such as a continuous lowering of blood pressure, sympathicotonic-type electrocardiogram (ECG), depression-like behaviors, and hyperalgesia (Ohara et al, 1991). In this model, animals (usually mice) are kept in a room at a temperature alternating between 24 and 4C every hour in the day time, and then kept at 4C overnight.…”