McKay LC, Feldman JL (2008) Unilateral ablation of preBotzinger Complex disrupts breathing during sleep but not wakefulness. Am J Respir Crit Care Med 178(1):89-95. doi: 10.1164/rccm.200712-1901OC

Summary: Previous data has shown that ablation of preBötzinger complex (preBötC) neurokinin 1 expressing (NK1R) neurons disrupts breathing patterns in both sleep and wakefulness. The initial disruption is during sleep, with the eventual onset of ataxic breathing while the animals are awake. Here rats received a unilateral injection of SP-SAP (Cat. #IT-07, 6.7 ng) into the left preBötC. SP plus unconjugated saporin (Cat. #PR-01) was used as a control. Unilaterally treated rats did not develop disrupted breathing patterns during wakefulness.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)

Young EE, Baumbauer KM, Hillyer JE, Patterson AM, Hoy KC, Jr., Mintz EM, Joynes RL (2008) The neonatal injury-induced spinal learning deficit in adult rats: central mechanisms. Behav Neurosci 122:589-600. doi: 10.1037/0735-7044.122.3.589

Summary: This report examined whether neonatal injuries had any contralateral effects in adult life, and evaluated the role of the NK1 receptor of adult animals that had been subjected to neonatal trauma. Rats were injected with 5 µl of SP-SAP (Cat. #IT-07, 30 ng/µl, 100 ng/µl, or 300 ng/µl) into the intrathecal space. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate both that injury effects are isolated in the injured limb, and NK1 receptor-expressing cells are involved in processing this pain.

Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)

Rahman W, Suzuki R, Hunt SP, Dickenson AH (2008) Selective ablation of dorsal horn NK(1) expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. Neuropharmacology 54:1208-1214. doi: 10.1016/j.neuropharm.2008.03.014

Summary: In this work the spinal origin of the major descending noradrenergic inhibitory pathway is examined with the help of SP-SAP (Cat. #IT-07). Rats received a 10-µl infusion of 1-mM SP-SAP (saporin, Cat. #PR-01, was used as a control) into the sub-arachnoid space terminating in the L4-5 region. Results from examining neuronal responses under the influence of the alpha2-adrenoceptor antagonist atipamezole suggest that NK1 expressing cells are involved with activity in noradrenergic pathways and descending facilitation.

Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)

Wiley RG (2008) Substance P receptor-expressing dorsal horn neurons: Lessons from the targeted cytotoxin, substance P-saporin. Pain 136:7-10. doi: 10.1016/j.pain.2008.03.010

Summary: This review covers some of the more recent work utilizing SP-SAP (Cat. #IT-07) and SSP-SAP (Cat. #IT-11) in the dorsal horn. Specific answers to experimental questions are discussed, as well as some of the questions generated by the research. The potential of SP-SAP and SSP-SAP as pain therapeutics is also explored, along with potential clinical applications of other targeted toxins in pain therapy.

Related Products: SP-SAP (Cat. #IT-07), SSP-SAP (Cat. #IT-11)

Haller J, Toth M, Zelena D, Halasz J (2007) Molecular basis of violent behavior: The role of NK1 receptors. Neuroscience 2007 Abstracts 531.22/GGG24. Society for Neuroscience, San Diego, CA.

Summary: Background. Neurons expressing Neurokinin1 receptor (NK1 or Substance P receptor) are abundant in limbic areas crucial for different emotional behaviors. In recent years, NK1 receptor blockers were proposed for the treatment of anxiety and depression. Moreover, in two different laboratory models, NK1 receptor blockade was successfully used to decrease violent components of aggression related behaviors in Wistar rats (Biol. Psychiatry, 2007, in press). In the above study, the NK1 receptor blockade reduced the number of more violent hard bites, while the number of soft bites was unaltered. Aggressive encounters were accompanied by a marked activation of neurons expressing NK1 receptors in the medial amygdala and in the hypothalamic attack area, where the highest number and proportion of activated NK1 positive neurons were found. Aim / Methods. We evaluated the precise role of neurons expressing NK1 receptors in the hypothalamic attack area during resident/intruder test. These neurons were selectively eliminated by a Substance P conjugated saporin bilateral microinjection into the hypothalamic attack area. After a week recovery, lesioned and vehicle treated control residents were faced with a smaller untreated opponent in their home cages for 20 min. The brains of the residents were later removed to assess the site of injection and the extent of the lesion. Results. In lesioned Wistars, the bilateral microinjection resulted in a complete and selective disruption of NK1 positive neurons in the hypothalamic attack area. Compared to vehicle injected controls, the number of hard bites toward unfamiliar residents showed a marked decrease (almost a complete abolition) in the lesioned group. The latency of hard bites was significantly increased compared to vehicle injected controls. The number of bite attacks was also reduced, but this reduction was mainly secondary to the dramatic reduction in the number of hard bites. Conclusions. Our data show that hypothalamic neurons expressing NK1 receptors are involved in the control of aggressiveness, especially in the expression of violent attacks. These data confirm and support earlier results that NK1 antagonists – beyond anxiety and depression – may also be useful in the treatment of aggressiveness and violence.

Related Products: SP-SAP (Cat. #IT-07)

Masawaki A, Sugiyo S, Shimoda T, Sakai Y, Ohyamaguchi A, Uehashi D, Moritani M, Yoshida A, Niwa H, Takemura M (2007) Effects of systemic bicuculline on the formalin-induced nociceptive response in the lip and c-Fos expression in the SP-Saporin-treated rats. Neuroscience 2007 Abstracts 186.16/RR16. Society for Neuroscience, San Diego, CA.

Summary: This study examines the effect of systemic bicuculline (2 mg/kg, ip) on formalin-induced pain-related behavior in the lip (PRB; face scrubbing behavior) and c-Fos expression in the trigeminal nucleus caudalis (SpVc) 2hrs after formalin injection and 2-4 weeks after intra cisterna magna (i.c.m.) injection of substance P (SP) conjugated to neurotoxin, saporin (SP-Sap; 3 µM, 5 µl), blank-Sap- or saline-treatment. In SP-Sap-treated rats, the number of NK-1- immunoreactive (NK-1-IR) neurons in lamina I of the SpVc decreased compared with that of saline- or blank-Sap-treated rats. In SP-Sap-treated rats, PRB at phase 2 decreased compared with that of saline- or blank-Sap-treated rats. In SP-Sap-treated rats, the number of c-Fos-IR cells in the VcI/II decreased compared with that in the saline- or blank-Sap-treated rats. In saline- and blank-Sap- treated rats but not SP-Sap-treated rats, systemic bicuculline decreased the number of PRB at phase 2. These results indicate that i.c.m. injection of SP-Sap eliminates NK-1-bearing neurons in L1 of SpVc, and that NK-1-bearing neurons in the SpVc have pivotal role in formalin-induced PRB at phase 2 and c-Fos expression in the SpVc. The decremental effects of systemic bicuculline on the formalin-induced nociceptive responses at phase 2 and c-Fos expression in the VcI/II are secure in the presence of NK-1 receptor bearing neurons in the Vc.

Related Products: SP-SAP (Cat. #IT-07)

Khan IM, Wart CV, Singletary EA, Stanislaus S, Deerinck T, Yaksh TL, Printz MP (2008) Elimination of rat spinal substance P receptor bearing neurons dissociates cardiovascular and nocifensive responses to nicotinic agonists. Neuropharmacology 54(2):269-279. doi: 10.1016/j.neuropharm.2007.09.014

Summary: Nocifensive behavior and cardiovascular responses due to nicotinic agonists may be sustained by substance P-positive primary afferents. Rats received 10-µl intrathecal injections of 10 µM SP-SAP (Cat. #IT-07); unconjugated saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reduced nocifensive response to nicotinic agonists. Tachycardia and pressor responses were enhanced upon administration of cytisine and epibatidine.

Related Products: Saporin (Cat. #PR-01), SP-SAP (Cat. #IT-07)

Caudle RM (2007) Featured Article: Inducing central sensitization with a substance P/ cholera toxin conjugate. Targeting Trends 8(4)

Related Products: SP-SAP (Cat. #IT-07), SP-CTA (Cat. #IT-39)

Read the featured article in Targeting Trends.

See Also:

• Caudle RM Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin. BMC Neuroscience 8:30, 2007.

Bavis RW, Powell FL, Bradford A, Hsia CCW, Peltonen JE, Soliz J, Zeis B, Fergusson ED, Fu Z, Gassmann M, Kim CB, Maurer J, McGuire M, Miller BM, O’Halloran KD, Paul RJ, Reid SG, Rusko HK, Tikkanen HO, Wilkinson KA (2007) Respiratory plasticity in response to changes in oxygen supply and demand. Integ and Comp Biol 47(4):532-551. doi: 10.1093/icb/icm070

Summary: This paper covers data presented at the First Annual Congress of Respiratory Biology. One of the subjects discussed is the use of SP-SAP (Cat. #IT-07) to elucidate the role of central chemoreceptors in the nucleus tractus solitarius during ventilatory acclimatization to hypoxia.

Related Products: SP-SAP (Cat. #IT-07)

Rahman W, Sikander S, Suzuki R, Hunt SP, Dickenson AH (2007) Superficial NK1 expressing spinal dorsal horn neurones modulate inhibitory neurotransmission mediated by spinal GABA(A) receptors. Neurosci Lett 419:278-283. doi: 10.1016/j.neulet.2007.04.039

Summary: It has been shown that elimination of lamina 1 NK1 receptor-expressing neurons affects pain behaviors. The authors investigated whether eliminating these neurons would alter GABAergic spinal inhibitory systems. Rats received 10-µl injections of 10-µM SP-SAP (Cat. #IT-07) into the L4-5 regions. Data generated by electrical and mechanical stimuli suggest that although GABAergic transmission is dependent on NK1 receptor-expressing neurons, loss of these cells results in a decrease in spinal cord excitability.

Related Products: SP-SAP (Cat. #IT-07)