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Activity of motoneurons during fictitious scratch reflex in the cat.

(1) Intracellular recording of motoneurons of different hindlimb muscles: tibialis anterior (TA), gastrocnemius and soleus (GS), vastus crureus (Vast), posterior biceps and semitendinosus (PBSt), was carried out during the fictitious scratch reflex in decerebrate cats. (2) During the postural stage of the reflex, a depolarizaiton (3.8 mV on average) was observed in TA motoneurons accompanied by tonic discharge. No change of the membrane potential (MP) and no discharge were observed during this stage in GS, Vast and PBSt motoneurons. (3) In the rhythmical stage of the reflex, the MP of TA motoneurons changed only slightly during the 'long' (L) phase of the scratch cycle and remained at approximately the same level as during the postural stage. In this phase, motoneurons discharged at frequencies of 20-100 pps. In the 'short' (S) phase of the scratch cycle a strong repolarization occurred, the MP reached the same level as observed during resting conditons (MP0), and the discharge discontinued. (4) GS motoneurons were gradually depolarized during the second half of the L-phase. The depolarization reached its maximum (5.5 mV on average in relation to the MP0) on average in relation to the MP0) in the S-phase, and several action potentials were generated with intervals of 5-10 msec. Then, at the beginning of the L-phase, the motoneurons were repolarized and the MP reached the level of the MP0. The behavior of Vast motoneurons was essentially similar to that of GS motoneurons. (5) The PBSt motoneurons usually had two peaks of depolarization per cycle--in the S-phase and at the beginning of the L-phase. The maximal depolarization was 3.5 mV (on average). The motoneurons generated action potentials at one or both peaks of depolarization. (6) The possible organization of the central influences upon motoneurons of different muscles during scratching is discussed.

Afferent Pathways↗

Activity of Ia inhibitory interneurons during fictitious scratch reflex in the cat.

(1) The fictitious scratch reflex was observed in decerebrate cats immobilized with Flaxedil. The activity of interneurons in the inhibitory pathways from Ia afferents to motoneurons of antagonistic muscles was recorded during scratching. The selected interneurons were supplied by Ia afferents from m. vastus, posterior biceps-semitendinosus and sartorius. (2) Almost all recorded interneurons showed periodic modulation of activity. Their maximal activity in the scratch cycle usually coincided with the maximal activity of motoneurons of those muscles from which the interneurons receive Ia afferents. Excitation of Ia afferents by passive stretch of the muscle or by electrical stimulation of the muscle nerve resulted in the increase of the interneuron activity, without changing its timing in the scratch cycle.

Afferent Pathways↗

Activity of neurons of cerebellar nuclei during fictitious scratch reflex in cat. I. Fastigial nucleus.

The activity of neurons located in the rostral part of the fastigial nucleus was recorded during the fictitious scratch reflex in thalamic cats immobilized with Flaxedil. The activity of most of the neurons was rhythmically modulated in relation to the scratch cycle: they generated bursts of impulses separated by periods of silence or, in a few cases, by periods of reduced activity. The discharge pattern of neurons was usually the same during both ipsilateral and contralateral scratch reflex: in both cases their maximum activity could be observed in the extensor phase of the scratch cycle. Rhythmical modulation of fastigial neurons is determined by signals coming from the central spinal mechanism, generating rhythmical oscillations, via the ventral spinocerebellar tract (VSCT) and the spinoreticulo-cerebellar pathway (SRCP). Results of separate transections of these pathways suggest that the SRCP determines the periodical excitationm of fastigial neurons and the VSCT their periodical inhibition.

Afferent Pathways↗

Effects of stimulation of midline inhibitory area within the pontine tegmentum on scratch reflex.

Effects of stimulation of the midline inhibitory area of the dorsal tegmental field (DTF) in the pons on the fictive scratch reflex were studied in decerebrate immobilized cats. The fictive scratch reflex was evoked by tactile stimulation of the pinna. DTF stimulation suppressed both the scratch-related rhythmical activities of the nerves (ENGs) supplying m. lateralis gastrocnemius and m. tibialis anterior, and of the interneurons at the 'leading' area of the spinal cord (L5 segment) where the scratch rhythm generator is presumably located.

Animals↗

A novel synthetic phyllolitorin analogue [desTrp3,Leu8]phyllolitorin inhibits scratching behavior induced by neuromedin C in rats.

[DesTrp3,Leu8]phyllolitorin (DTP) (pGlu-Leu-Ala-Val-Gly-Ser-Leu-Met-NH2) was synthesized as an analogue of phyllolitorins, a new member of bombesin family, and examined if it antagonized neuromedin C (NMC)-induced scratching. DTP inhibited dose-dependently the scratching behavior by NMC (1 microgram), whereas it did not alter any element of other grooming behaviors. DTP (6 micrograms) alone was found to be neither toxic nor active in inducing both scratching and grooming, which were comparable to vehicle alone. Assuming that the scratching behavior is commonly and specifically elicited by bombesin family peptides, DTP might be classified as a new type of bombesin antagonist.

Amino Acid Sequence↗

Influence of NMDA receptor ligands on thyrotropin-releasing hormone-induced scratching in rabbits.

The influence of intracaudate administration of N-methyl-D-aspartic acid (NMDA) and of the competitive NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (AP-5) was studied on thyrotropin-releasing hormone (TRH)-induced scratching in rabbits. NMDA (28 nmol) significantly increased the latency of TRH-induced scratching but did not modify the duration of this behaviour. Conversely, AP-5 (0.5 mumol) significantly potentiated scratching duration. Since TRH-induced scratching has been reported to be a dopamine-dependent behaviour, these results suggest that NMDA receptor ligands modulate dopaminergic neurotransmission.

2-Amino-5-phosphonovalerate↗

Plasma from patients with the pruritus of cholestasis induces opioid receptor-mediated scratching in monkeys.

The medullary dorsal horn is a site of action of opiates in producing facial scratching. Extracts of plasma (0.4 microliter) from 4 patients with the pruritus of cholestasis induced facial scratching when microinjected into the medullary dorsal horn of monkeys. This extract-induced scratching could be abolished or prevented by administering the opioid receptor antagonist, naloxone. Neither saline nor an extract of plasma from a nonpruritic cholestatic patient induced scratching when similarly administered. We infer that plasma of patients with the pruritus of cholestasis contains a factor which induces pruritus by a central opioid receptor-mediated mechanism.

Adolescent↗

Blockage of substance P-induced scratching behavior in rats by the intrathecal administration of inhibitory amino acid agonists.

Intrathecal administration of 20 micrograms of substance P induced scratching behavior in most tested rats (80%). Scratching appeared in bouts of short latency and variable duration, intensity and frequency (range 1-60, mean number of scratching bouts in one hour test: 8.93 +/- 1.86). Intrathecal administration of glycine (400 micrograms but not 66 micrograms) significantly decreased the effect of substance P on this behavior. Taurine, in dosages equimolar to glycine, abolished the response to substance P at the high dose level (700 micrograms), but did not significantly affect it at the lower level (120 micrograms). The GABAA agonist, muscimol, abolished the effect of substance P at the 3 micrograms dose level, but the 0.5 microgram dose did not produce a significant effect. Baclofen, a GABAB agonist, was highly effective in significantly reducing the action of SP at 0.9 and 0.15 microgram; only two of 8 rats receiving the low dose of baclofen (0.15 microgram) exhibited scratching. The results suggest that the spinal inhibitory amino acids modulate nociceptive impulses generated by the action of substance P in dorsal horn neurons of the spinothalamic tract.

Animals↗

Opioid inhibition of kainic acid-induced scratching: mediation by mu and sigma but not delta and kappa receptors.

Scratching induced by intrathecal (IT) administration of kainic acid (0.5 nmol) to rats was inhibited by IT pretreatment with the selective mu agonists levorphanol (30 and 90 nmol), [D-Ala2,N-Met-Phe4,Gly5-ol]-enkephalin (DAGO, 0.4 and 1.1 nmol), or morphine (90 nmol), the mixed mu-delta agonist [D-Ala2,D-Leu5]-enkephalinamide (DADLE, 10 and 30 nmol), or the sigma/phenycyclidine (PCP) agonists dextrorphan (90 nmol) or (+)-N-allyl-N-normetazocine ([+]-NAM, 90 nmol). The kappa agonists dynorphin (1.1 nmol) and ethylketocyclazocine (EKC, 90 nmol) had no significant effect, nor did the selective delta agonist [D-Pen2,D-Pen5]-enkephalinamide (DPDPE, 90 nmol). The nonopioids (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([+]-3-PPP, 90 nmol) and PCP (90 nmol), selective for sigma and PCP sites, respectively, both antagonized kainic-induced scratching. Levorphanol- and DADLE-induced attenuation of scratching was partially antagonized by naltrexone. These findings suggest that opioid inhibition of kainic acid-induced scratching is mediated by classical mu receptors as well as sigma and PCP sites.

Animals↗

Scratching as a behavioral index of anxiety in macaque mothers.

The aim of this study was to assess the validity of the notion that anxiety influences maternal style in monkeys. To this end, we investigated the correlations between measures of the quality of mother-infant relationship and scratching, a behavior pattern that reflects a state of anxiety. The subjects were seven group-living macaque mothers and their infants observed during the first 12 weeks postpartum. Postpartum scratching by the mothers was positively correlated with both maternal possessiveness and maternal warmth, two composite measures of the quality of mother-infant relationship that reflect a possessive and attentive maternal style. Evaluation of the correlations between maternal rank and scratching before and after parturition indicated that interactions with their infants, not those with other group companions, were the main source of anxiety for the mothers. These results support the notion that anxiety influences maternal style in monkeys and suggest that studies aimed at investigating physiological and social correlates of maternal emotionality in nonhuman primates could use scratching as a useful and simple behavioral measure.

Animals↗

Stimulation of the nucleus paraventricularis thalami suppresses scratching and biting behaviour of arthritic rats and exerts a powerful effect on tests for acute pain.

In 20 arthritis-sensitive Wistar rats, an electrode was implanted in the paraventricular thalamic nucleus (PV). In the tail-flick and hot-plate test, PV was stimulated continuously for a period of 30 min, during which every 5 min either a tail-flick or hot-plate test was performed. Stimulation of PV induced important prolongations of the reaction times on tail-flick and hot-plate tests. However, there was no significant correlation between the results of the two tests. The effect of stimulation was immediate and did not outlast the stimulation period. PV stimulation did not give rise to tolerance, either within the stimulation period of 30 min, or during the successive testing days. After the termination of these acute pain tests, rats were inoculated with Mycobacterium butyricum. All animals developed polyarthritis. PV stimulation had a profound suppressive effect on the scratching and biting behaviour displayed by the animals. This reduction in scratching and biting behaviour was specific for PV stimulation since stimulation of another target, the ventrolateral thalamic nucleus (4 animals), had no effect on these behaviours. The attenuation of the scratching and biting behaviour was not a result of a general motor impairment, since other behaviours increased (running and sniffing) or did not change. There was no significant correlation between the results of scratching behaviour with those of the tail-flick and hot-plate test.

Animals↗

Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system.

The role of central mu- and kappa-opioid receptors in the regulation of itch sensation was examined using pruritogen-induced mouse scratching behavior model. Intracerebroventricular administration of beta-funaltrexamine, a selective mu-opioid receptor antagonist, inhibited the scratching behavior induced by intradermal substance P, but subcutaneous administration of beta-funaltrexamine did not. Similarly, the scratching inhibitory activity of subcutaneously administered TRK-820, (-)-17-(cyclopropylmethyl)-3, 14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl) acrylamido] morphinan hydrochloride, a kappa-opioid receptor agonist, was antagonized by intracerebroventricular administration of nor-binaltorphimine (10 microg/site), a kappa-opioid receptor antagonist, but was not by subcutaneous administration of nor-binaltorphimine. In addition, the scratching induced by the direct activation of central mu-opioid receptor by intracisternal morphine was significantly and dose-dependently inhibited by subcutaneous administration of TRK-820. Taken all together, it is suggested that the central mu-opioid receptors play a role in the processing of itch sensation, and the activation of central kappa-opioid receptors antagonize the central mu-opioid receptor mediated itch processing, thereby suppressing itch sensation.

Animals↗

Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2.

We examined whether the proteinase-activated receptor-2 (PAR2) agonist, H-Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL-NH2), could induce scratching behavior in mice. Intradermal injections of SLIGRL-NH2 (10-50 microg) evoked dose dependent scratching. This behavior peaked near 5 min and returned to preinjection levels within 30 min. Pretreatment of animals with a histamine H1 receptor antagonist, pyrilamine, blocked histamine induced scratching, but it had little effect on SLIGRL scratching. Our study suggests that PAR2 mediates histamine independent itch.

Animals↗

Inhibitory effects of TRK-820 on systemic skin scratching induced by morphine in rhesus monkeys.

The inhibitory effects of kappa-opioid receptor agonists on systemic skin scratching induced by the intravenous administration of morphine, a micro-opioid receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment with kappa-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 microg/kg or U-50488H at 64 and 128 microg/kg, inhibited systemic skin scratching induced by morphine at 1 mg/kg, i.v. in a dose-dependent manner. By the intragastric route, apparent inhibitory effects on morphine-induced systemic skin scratching were evident following pretreatment with TRK-820 at 4 microg/kg but not with U-50488H from 512 to 2048 microg/kg. These results suggest that TRK-820 produces antipruritic effects on i.v. morphine-induced systemic skin scratching and is more readily absorbed intragastrically than is U-50488H, resulting in high bioavailability in the intragastric route.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Intrathecal administration of the common carboxyl-terminal decapeptide in endokinin A and endokinin B evokes scratching behavior and thermal hyperalgesia in the rat.

Endokinins are novel mammalian tachykinin peptides designated from a human preprotachykinin gene and consist of endokinin A (EKA), endokinin B (EKB), endokinin C (EKC) and endokinin D (EKD). A representative of the tachykinin peptide is substance P (SP), which functions as a pain modulator or transmitter and contributes to pain processing; however, little is known about the function of endokinins in pain processing. Therefore, we evaluated the effects of EKA/B (using the common C-terminal decapeptide in EKA and EKB) and EKC/D (using the common C-terminal duodecapeptide in EKC and EKD) on pain processing in rats. Intrathecal administration of 10(-3) M (10 nmol) EKA/B evoked pain-related behavior such as scratching while 10(-3) M EKC/D administration did not. This induction of scratching behavior following EKA/B administration was suppressed by pretreatment with an NK1 receptor antagonist. In addition to the induction of scratching behavior, intrathecal administration of 10(-7) - 10(-4) M (1 pmol-1 nmol) EKA/B decreased the latency of the paw withdrawal response to noxious thermal stimulation, whereas there was little effect of EKC/D administration on the latency of the withdrawal response. This effect of EKA/B was also suppressed by pretreatment with NK1 receptor antagonists. These results indicate that intrathecal administration of EKA/B but not EKC/D evokes scratching behavior and thermal hyperalgesia through the NK1 receptor.

Animals↗

Pentacyclic triterpenoids, alpha,beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.

In the search for natural compounds useful against pruritus, alpha,beta-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant Protium heptaphyllum were examined on scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with alpha,beta-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with alpha,beta-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with alpha,beta-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, alpha,beta-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of alpha,beta-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.

Analgesics, Opioid↗

Effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior in mice.

The effects of histamine H1 receptor antagonists on compound 48/80-induced scratching behavior were studied in mice. Classical histamine H1 receptor antagonists such as diphenhydramine and chlorpheniramine caused a potent depressant effect on compound 48/80-induced scratching behavior. Histamine H1 receptor antagonists having antiallergic activity (an inhibition of mast cell degranulation), such as azelastine and oxatomide and nonsedative histamine H receptor antagonists such as terfenadine, epinastine and astemizole, also showed a relatively potent effect. On the other hand, the effects of tranilast and cromolyn sodium--antiallergic drugs without histamine H1 receptor antagonistic activity--were extremely weak. Diazepam had weak or no depressant effects on compound 48/80-induced scratching behavior. These results suggest that inhibition of compound 48/80-induced scratching behavior is mainly due to histamine H1 receptor antagonistic activity and not to the sedative action of the drugs.

Animals↗

Lichen amyloidosus: a consequence of scratching.

BACKGROUND: Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes. OBJECTIVE: Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA. METHODS: We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment. RESULTS: In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective. CONCLUSION: LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Administration, Cutaneous↗