Differential Contribution of 5-HT, 5-HT, and 5-HT Receptors to Acute Pruriceptive Processing Induced by Chloroquine and Histamine in Mice.

The involvement of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing in the central nervous system (CNS) has been reported using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the roles of 5-HT receptor family in acute pruriceptive processing have not been fully elucidated in the CNS. In the present study, scratching behavior induced by chloroquine (CQ) was ameliorated by milnacipran or mirtazapine, and these effects were reversed by SB207266, a 5-HT antagonist, or SB258585, a 5-HT antagonist, but not by SB258585, a 5-HT antagonist. Moreover, CQ-induced scratches were mitigated by intrathecal injection of 5-HT agonists, such as BIMU8 and ML10302, and the 5-HT agonist, WAY208466.

Role of kainate receptors in pruriceptive processing in the mouse spinal cord.

Pruritus, including neuropathic and psychogenic pruritus, is an unpleasant feeling that causes a desire to scratch, which negatively impacts physical and psychological aspects of daily life. Nonetheless, little is known about the neural mechanisms involved in pruritus. Glutamate is a predominant excitatory neurotransmitter in the mammalian central nervous system and exerts its effects by binding to various glutamate receptors, including kainate (KA) receptors; however, the precise involvement of each glutamate receptor in pruriceptive processing remains unclear, particularly that of KA receptors.

Time course of effects of venlafaxine on migraine and generalized pruritus in a patient with depression.

Venlafaxine has potential as a therapeutic option for patients with depressive disorder, migraine, and pruritus unresponsive to antihistamines.

Roles of 5-HT and 5-HT receptors in acute pruriceptive processing in mice.

The roles of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing have been demonstrated using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the involvement of 5-HT in acute pruriceptive processing has not yet been elucidated in detail. Scratching events induced by chloroquine (CQ) were attenuated by the administration of milnacipran or mirtazapine, and these effects were reversed by a treatment with ondansetron, a 5-HT antagonist, or SB26970, a 5-HT antagonist. CQ-induced scratching events were also ameliorated by the intrathecal administration of 5-HT, SR572227A and RS56812 (5-HT agonists), and LP211 and LP44 (5-HT agonists), indicating the modulation of CQ-induced scratching events by 5-HT and noradrenaline.

Differential onset time of mirtazapine on pruritus and depression in a patient receiving hemodialysis.

A 63-year-old male receiving hemodialysis for renal insufficiency developed severe and widespread pruritus, which was unresponsive to antihistamines and severe depression with insomnia, agitation, and anxiety. The oral administration of 7.5 mg mirtazapine daily alleviated his severe pruritus after 4 days and severe depression after 14 days.

Perampanel attenuates scratching behavior induced by acute or chronic pruritus in mice.

An itch is defined as an unpleasant sensation that evokes a desire to scratch. Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system and has a crucial role in pruriceptive processing in the spinal dorsal horn. It is well known that glutamate exerts its effects by binding to various glutamate receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and that AMPA/kainate receptors play a crucial role in pruriceptive processing; however, the precise role of AMPA receptors remains uncertain.

Serotonin and noradrenaline modulate chronic itch processing in mice.

The roles of serotonin and noradrenaline in the modulation of chronic pruriceptive processing currently remain unclear. To clarify the contribution of serotonin and noradrenaline to chronic itch, the effects of the administration of antidepressants or noradrenaline reuptake inhibitors were evaluated in the present study. A pretreatment with milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, attenuated the induction of spontaneous scratching behavior in mice with chronic itch.

Pharmacological characteristics of hemokinin-1-derived peptides in rat pruriceptive processing.

Hemokinin-1 (HK-1) is a member of mammalian tachykinin peptide family, and [Leu]-HK-1 has an antagonistic effect on HK-1. The attenuation of pruritogen-induced scratching behavior by pretreatment with [Leu]-HK-1 indicates the involvement of HK-1 in pruriceptive processing. However, it remains unclear whether the intrathecal or intranasal administration of HK-1-derived peptides, such as [D-Trp]-[Leu]-HK-1 or [D-Trp]-[Leu]-HK-1, elicits the effects different from [Leu]-HK-1.

Role of serotonin and noradrenaline in the acute itch processing in mice.

The contribution of serotonin and noradrenaline to the modulation of pruriceptive processing was evaluated by administrating antidepressants or noradrenaline reuptake inhibitors. The pretreatment with milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, attenuated the induction of scratching behavior by chloroquine, a representative pruritogen, indicating the involvement of serotonin and/or noradrenaline in the modulation of pruriceptive processing. By contrast, the single administration of noradrenaline reuptake inhibitor such as atomoxetine and nisoxetine or serotonin reuptake inhibitor such as fluvoxamine and escitalopram had little effect on chloroquine-induced scratching, whereas the induction of scratching behavior by chloroquine was significantly ameliorated by co-administration of serotonin reuptake inhibitors and noradrenaline reuptake inhibitors.

Alleviation of thalamic pain by cilostazol administration: a case report.

Thalamic pain is severe and treatment-resistant; however, there are few available options for improving thalamic pain. This study demonstrated that thalamic pain was alleviated by administration of cilostazol, suggesting that cilostazol may be a candidate for treating thalamic pain.

Distribution of hemokinin-1 in the rat trigeminal ganglion and trigeminal sensory nuclear complex.

Objective: A new mammalian tachykinin peptide encoded in a TAC4 gene was identified and designated as hemokinin-1 (HK-1). A representative of the tachykinin peptide family is substance P (SP), and the function of SP has been well characterized as a pain transmitter or modulator, while it is possible that HK-1 is involved in pruriceptive processing, but, as yet, the distribution of HK-1 peptide in the trigeminal sensory system is still unknown. Thus, the aim of the present study was to elucidate the distribution of HK-1, while comparing the expression of SP, in the trigeminal ganglion and trigeminal sensory nuclear complex.

Effects of cabergoline and rotigotine on tacrine-induced tremulous jaw movements in rats.

Objectives: We examined the effects of two dopamine agonists, cabergoline and rotigotine, on tacrine-induced tremor and c-Fos expression in rats.

Methods: Rats received intraperitoneal injection of cabergoline (0.5, 1.

The role of spinal serotonin receptor and alpha adrenoceptor on the antiallodynic effects induced by intrathecal milnacipran in chronic constriction injury rats.

Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran.

Intrastriatal grafts of fetal ventral mesencephalon improve allodynia-like withdrawal response to mechanical stimulation in a rat model of Parkinson's disease.

We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments.

Effect of blonanserin on methamphetamine-induced disruption of latent inhibition and c-Fos expression in rats.

To clarify the psychopharmacological profile of blonanserin, a novel antipsychotic, we examined its effect on the methamphetamine-induced disruption of latent inhibition (LI) and the neural activation related to this effect in rats. To evaluate the LI, we used a conditioned emotional response in which a tone (conditioned stimulus) was paired with a mild foot shock (unconditioned stimulus). This paradigm was presented to rats licking water.

Pharmacological characteristics of endokinin C/D-derived peptides in nociceptive and inflammatory processing in rats.

Endokinins designated from the human TAC4 gene consist of endokinin A, endokinin B, endokinin C (EKC) and endokinin D (EKD). EKC/D is a peptide using the common carboxyl-terminal in EKC and EKD and consists of 12 amino acids, and exerts antagonistic effects on the induction of scratching behavior by substance P (SP). Some of SP-preferring receptor antagonists have several d-tryptophan (d-Trp); however, the pharmacological effect of EKC/D-derived peptides with d-Trp remains to be solved.

Knockdown of the tachykinin neurokinin 1 receptor by intrathecal administration of small interfering RNA in rats.

The contribution of tachykinin neurokinin 1 (NK₁) receptor to nociceptive processing in the dorsal horn has been evaluated by tachykinin NK₁ receptor antagonism and knockout or knockdown of tachykinin NK₁ receptor; however, these results have not always been consistent. Therefore, to reevaluate the role of tachykinin NK₁ receptor in the dorsal horn, a solution of hemagglutinating virus of the Japan envelope (HVJ-E) with small interfering RNA (siRNA) against tachykinin NK₁ receptor was administered intrathecally and then the effect of treatment on tachykinin NK₁ receptor immunohistochemistry and on the induction of inflammation, thermal hyperalgesia and scratching behavior was evaluated. This treatment resulted in marked reduction of tachykinin NK₁ receptor immunoreactivity through the spinal dorsal horn, and the induction of thermal hyperalgesia and scratching behavior by substance P was significantly attenuated in rats with tachykinin NK₁ receptor siRNA.

Differential expression of FosB, c-Fos, and Zif268 in forebrain regions after acute or chronic L-DOPA treatment in a rat model of Parkinson's disease.

A study was carried out to examine the effects of acute and chronic L-DOPA treatment on the distribution of the immediate-early gene (IEG) proteins (FosB, c-Fos, and Zif268) in forebrain regions in a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. During a course of chronic L-DOPA treatment (15 mg/day, 15 days), rats with a 6-OHDA lesion developed abnormal involuntary movements. Compared with the rats in the acute L-DOPA treatment group, those in the chronic treatment group had significantly more FosB-immunopositive cells in the anterior cingulate (Cg) and the dorsolateral caudate-putamen ipsilateral to the lesion and significantly fewer c-Fos-immunopositive cells in the Cg, the nucleus accumbens shell, and the basolateral nucleus of amygdala ipsilateral to the lesion.

Subcutaneous injection of endokinin C/D attenuates carrageenan-induced inflammation.

Endokinins, encoded by the human preprotachykinin C (PPT-C)/TAC4 gene, are peptides that consist of endokinin A (EKA), B (EKB), C (EKC) and D (EKD) and belong to the tachykinin family. Intrathecal injection of EKC/D (using the common carboxyl-terminal duodecapeptide in EKC and EKD) markedly attenuated the induction of thermal hyperalgesia and scratching behavior by intrathecal administration of substance P (SP), indicating that EKC/D has an antagonistic effect on the neurokinin 1 receptor (NK1R), SP-preferring receptor, at the spinal level; however, the pharmacological function of EKC/D at the periphery is not yet understood. Therefore, to clarify the effect of EKC/D on the peripheral tissue, the effect of subcutaneous injection of EKC/D on carrageenan-induced inflammation was examined.

NMDA and AMPA receptors contribute to the maintenance of substance P-induced thermal hyperalgesia.

It is well known that intrathecal administration of substance P (SP) induces thermal hyperalgesia, but the mechanisms underlying the maintenance of SP-induced thermal hyperalgesia remain to be clarified. Thus, to clarify the receptors involved in the maintenance of SP-induced thermal hyperalgesia, the effect of administering SP or glutamate receptor agonists, NMDA or AMPA, under SP-induced thermal hyperalgesia was investigated. Also, the effect of pretreatment with protein kinase inhibitors on scratching behavior by NMDA or AMPA under SP-induced thermal hyperalgesia was examined.

Differential effects of substance P or hemokinin-1 on transient receptor potential channels, TRPV1, TRPA1 and TRPM8, in the rat.

Two tachykinin peptides, substance P (SP) and hemokinin-1 (HK-1), and three transient receptor potential (TRP) channels, TRPV1, TRPA1 and TRPM8, are similarly localized in the spinal dorsal horn and dorsal root ganglion, suggesting that TRP channels may be related or modulated by these tachykinin peptides. Thus, to clarify whether the responses of TRP channels are modulated by SP or HK-1, the effects of pretreatment with SP or HK-1 on the induction of scratching behavior by TRP channel agonists were examined. Pretreatment with SP or HK-1 enhanced the induction of scratching behavior by resiniferatoxin, a TRPV1 agonist, whereas scratching behavior induced by menthol, a TRPM8 agonist, was suppressed by pretreatment with these peptides.

Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model.

The objective of the present study was to examine whether milnacipran, a serotonin-noradrenaline reuptake inhibitor, has an analgesic effect in rats with neuropathic pain. In addition, the c-Fos expression was investigated in the supraspinal sites of the brain and in the spinal dorsal horn in association with the nociceptive processing in rats with neuropathic pain produced by chronic constriction injury (CCI) in the sciatic nerve. In the CCI-induced neuropathic rats, behavioral testing for determining the change in the withdrawal threshold to mechanical stimulation and immunohistochemical detection of c-Fos were both performed.

Effect of the carboxyl-terminal of endokinins on SP-induced pain-related behavior.

The preprotachykinin C gene encodes four endokinins, A, B, C, and D. Endokinins A and B and substance P (SP) are typical tachykinin peptides since their carboxyl-terminal regions share an F-F-G-L-M-amide, while endokinins C and D share an F-Q-G-L-L-amide. It is demonstrated that pretreatment with a peptide consisting of a common sequence between endokinins C and D (EKC/D) attenuates the induction of scratching behavior and thermal hyperalgesia by intrathecal administration of SP or EKA/B (the carboxyl-terminal dacapeptide common in endokinins A and B), suggesting that leucine at the carboxyl-terminal of EKC/D may have a crucial role in eliciting these effects.

Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain.

Antidepressants, especially tricyclic antidepressants (TCAs) are widely used for the treatment of various types of chronic and neuropathic pain. The antinociceptive effects of TCAs are, however, complicated. Therefore, two kinds of newer antidepressants whose functions have been more fully clarified were selected, milnacipran, a serotonin and noradrenaline reuptake inhibitor (SNRI) and paroxetine and fluvoxamine, which are selective serotonin reuptake inhibitors (SSRIs).

Psychological prenatal stress reduced the number of BrdU immunopositive cells in the dorsal hippocampus without affecting the open field behavior of male and female rats at one month of age.

We examined whether prenatal psychological stress with little physical stress causes changes in the behavior and neurogenesis of the offspring of Sprague-Dawley rats at one month. Dams in the last trimester of gestation were psychologically stressed by placing them in a social communication box and shocking a rat on the other side of a transparent wall. They suffered little physical stress.