SSP-SAP References

Cat #IT-11

Molecular Neurosurgery with Targeted Toxins, edited by RG Wiley and DA Lappi

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Souza G, Kanbar R, Stornetta DS, Abbott SBG, Stornetta RL, & Guyenet PG. Breathing Regulation and Blood Gas Homeostasis after near Complete Lesions of the Retrotrapezoid Nucleus in Adult Rats. (2018). J Physiol2018/04/19.

Dose:  A total of 6 microinjections (120 nl/injection; 3 rostrocaudally aligned injections per side) were made 100-200 μm below the lower edge of the facial motor nucleus 2 mm lateral to the midline.  Experimental rats received either 0.6 ng, 1.2 ng, or 2.4 ng of SSP-SAP per injection.
Objective:  To test how important the retrotrapezoid nucleus (RTN) is to PCO2 homeostasis and breathing during sleep or wake.
Summary:  Near complete RTN destruction in rats virtually eliminates the CRC but HVR persists and sighing and the state-dependence of breathing are unchanged. Under normoxia, RTN lesions cause no change in VE but alveolar ventilation is reduced by at least 21%, probably because of increased physiological dead volume. RTN lesions do not cause sleep apnea during SWS, even under hyperoxia.

Strichartz G, Khasabov S, Barr T, Wang J, & Simone D. Modulation of Chronic Post-Thoracotomy Pain by Nk-1 Neurons in the Rostral Ventromedial Medulla Is Not Paralleled by Changes Spinal Mapkinase Activation. (2018). The Journal of Pain, 19 (3):S14.

Dose:  Ablation of Neurokinin-1 receptor (NK-1R)- expressing neurons in the rat rostral ventromedial medulla (RVM), by micro-injection of the specific neurotoxin SSP-SAP.
Objective:  To evaluate SSP-SAP in treatment of tactile hypersensitivity for Chronic Post-Thoractotomy Pain (CPTP).
Summary:  SSP-SAP 3 weeks before thoracotomy and rib retraction (TRR) was able to completely prevent CPTP, assayed by tactile hypersensitivity.

Araldi D, Ferrari LF, & Levine JD. Role of Gpcr (Mu-Opioid)-Receptor Tyrosine Kinase (Epidermal Growth Factor) Crosstalk in Opioid-Induced Hyperalgesic Priming (Type Ii). (2018). Pain 2018/02/16.

Dose:  SSP-SAP was prepared in saline (5 ng/mL), and 20 mL was injected intrathecally into rats, 14 days before nociceptive tests.
Objective:  To determine the the mechanisms mediating the induction of opioid-induced hyperalgesia and the prolongation of prostaglandinE2-induced hyperalgesia in type II hyperalgesic priming.
Summary:  Understanding the mechanisms responsible for the induction of type II hyperalgesic priming, a form of neuroplasticity in the peripheral terminal of the primary afferent nociceptor, may provide useful information for the design of drugs with improved therapeutic profiles to treat neuroplasticity induced by chronic use of opioids.

Ferrari LF, Khomula EV, Araldi D, & Levine JD. Cd44 Signaling Mediates High Molecular Weight Hyaluronan-Induced Antihyperalgesia. (2018). The Journal of Neuroscience, 38 (2):308-321.

Dose:  Both IB4-SAP and SSP-SAP were diluted in saline to doses previously shown to deplete nonpeptidergic (3.2 mcg/rat for IB4-SAP) and peptidergic (100 ng/rat for SSP-SAP) fibers.  The toxins were administered intrathecally, in a volume of 20 mcl, 14 d before intradermal injection of LMWH on the dorsum of the hindpaw.  Treatment with either conjugate, or a combination of the two, did not significantly affect mechanical nociceptive threshold.
Objective:  To study the role of  the cognate hyaluronan receptor, CD44, signaling in anti-hyperalgesia induced by high molecular weight hyaluronan (HMWH).
Summary:    These results demonstrate the central role of CD44 signaling in HMWH-induced anti-hyperalgesia, and establish it as a therapeutic target against inflammatory and neuropathic pain.



Fu C, Xue J, Wang R, Chen J, Ma L, Liu Y, Wang X, Guo F, Zhang Y, Zhang X, Wang S. (2017) Chemosensitive Phox2b-Expressing Neurons Are Crucial for Hypercapnic Ventilatory Response in the Nucleus Tractus Solitarius. J Physiol 595(14):4973-89. PMID: 28488367

Dose:   Two protocols were applied for SSP-SAP injections.  In immunostaining experiments, to determine how many Phox2b-containing cells were destroyed, a total volume of 100 nl of PBS containing 6 ng of SSP-SAP (3 ng in 50 nl; 2 injections) was injected into one side of the NTS and the contralateral NTS was used as a control (no injection).  For in vivo experiments, to determine whether loss of Phox2b cells led to impaired HCVR, bilateral injections with a total volume of 200 nl of PBS containing 6 ng (1.5 ng in 50 nl per injection; 2 injections per side) or 12 ng (3 ng in 50 nl per injection; two injections per side) of toxin into NTS.  Breathing was studied in conscious, freely moving mice treated with SSP-SAP and Blank-SAP.
Objective:  To investigate whether paired-like homeobox 2b  (Phox2b)-expressing NTS neurons are recruited in hypercapnic ventilatory response (HCVR)  and whether these neurons exhibit intrinsic chemosensitivity.
Summary:  Respiratory deficits caused by injection of SSP-SAP into the NTS are attributable to proportional lesions of CO2/H+-sensitive Phox2b-expressing neurons.

Yaksh TL, Fisher C, Hockman T, Wiese A. (2017) Current and Future Issues in the development of spinal agents for the management of pain. Curr Neuropharmacol 15(2):232-259. PMID: 26861470 (Targeting Trends 16q2)


Araldi D, Ferrari LF, Levine JD. (2016) Gi-Protein Coupled 5-HT1B/D Receptor Agonist Sumatriptan Induces Type I Hyperalgesic Priming. Pain 157(8):1773-82.PMID: 27075428 (Targeting Trends 16q3)

Gritsch S, Bali KK, Kuner R, Vardeh D. (2016) Functional characterization of a mouse model for central post-stroke pain. Molecular Pain 12:1744806916629049. PMID: (Targeting Trends 16q3)


Akiyama T, Nguyen T, Curtis E, Nishida K, Devireddy J, Delahanty J, Carstens MI, Carstens E. (2015) A central role for spinal dorsal horn neurons that express neurokinin-1 receptors in chronic itch. Pain 156(7):1240-1246. (Targeting Trends 15q3)

Kras JV, Weisshaar CL, Pall PS, Winkelstein BA. (2015) Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett 604:193-198. PMID: 26240991 (Targeting Trends 15q4)


Cordier D, Gerber A, Kluba C, Bauman A, Hutter G, Mindt TL, Mariani L. (2014) Expression of Different Neurokinin-1 Receptor (NK1R) Isoforms in Glioblastoma Multiforme: Potential Implications for Targeted Therapy. Cancer Biother Radiopharm 29(5):221-226. (Targeting Trends 14q2)

Feetham CH, Barrett-Jolley R. (2014) NK1-receptor-expressing paraventricular nucleus neurones modulate daily variation in heart rate and stress-induced changes in heart rate variability. PHY2 2(12):e12207. (Targeting Trends 15q1)

Takakura AC, Barna BF, Cruz JC, Colombari E, Moreira TS. (2014) Phox2b-expressing retrotrapezoid neurons and the integration of central and peripheral chemosensory control of breathing in conscious rats. Exp Physiol 99(3):571-585. (Targeting Trends 14q2)

Weisshaar CL, Winkelstein BA. (2014) Ablating Spinal NK1-Bearing Neurons Eliminates the Development of Pain and Reduces Spinal Neuronal Hyperexcitability and Inflammation From Mechanical Joint Injury in the Rat. J Pain 15(4):378-386. (Targeting Trends 14q2)


Fricks-Gleason AN, Keefe KA. (2013) Evaluating the Role of Neuronal Nitric Oxide Synthase-Containing Striatal Interneurons in Methamphetamine-Induced Dopamine Neurotoxicity. Neurotox Res 24(2):288-297. (Targeting Trends 13q3)

Khasabov SG, Simone DA. (2013) Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia. Neuroscience 250C:151-165. (Targeting Trends 13q4)

Talman WT, Lin LH. (2013) Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii. Auton Neurosci 175(1-2):9-16. (Targeting Trends 13q2)


Abbott SB, Kanbar R, Bochorishvili G, Coates MB, Stornetta RL, Guyenet PG. (2012) C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats. J Physiol 590(12):2897-2915. (Targeting Trends 12q3)

Choi JI, Koehrn FJ, Sorkin LS. (2012) Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn. Mol Pain 8(1):4. (Targeting Trends 12q2)

Coolen LM. (2012) A pivotal role of lumbar spinothalamic cells in regulation of ejaculation via intraspinal connections. Targeting Trends 13(3).

Lin LH, Nitschke Dragon D, Talman WT. (2012) Collateral damage and compensatory changes after injection of a toxin targeting neurons with the neurokinin-1 receptor in the nucleus tractus solitarii of rat. J Chem Neuroanat 43(2):141-148. (Targeting Trends 13q2)

Mishra SK, Holzman S, Hoon MA. (2012) A nociceptive signaling role for neuromedin B. J Neurosci 32(25):8686-8695. (Targeting Trends 12q4)

Staudt MD, Truitt WA, McKenna KE, de Oliveira CV, Lehman MN, Coolen LM. (2012) A Pivotal Role of Lumbar Spinothalamic Cells in the Regulation of Ejaculation via Intraspinal Connections. J Sex Med 9(9):2256-2265. (Targeting Trends 12q2)


King T, Porreca F (2011) Contribution of afferent pathways to nerve injury- induced spontaneous pain and evoked hypersensitivity. Targeting Trends 12(4):1, 2, 6.

King T, Porreca F. (2011) Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity. Targeting Trends 12(4).

Larsson M, Broman J. (2011) Synaptic plasticity and pain: role of ionotropic glutamate receptors. Neuroscientist 17(3):256-273. (Targeting Trends 11q3)

Sorkin LS, Choi J-I, Koehrn FJ. (2011) Carrageenan evoked P-Akt in deep dorsal horn neurons is prevented by loss of neurokinin1 positive neurons in superficial dorsal horn. Targeting Trends 12(2).

Wang Y, Mu X, Liu Y, Zhang X, Wu A, Yue Y (2011) NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might improve intractable visceral pain of cancer origin. Med Hypotheses 76(1):102-104. (Targeting Trends 10q4)

Wilkinson KA, Fu Z, Powell FL. (2011) Ventilatory Effects of Substance P-Saporin Lesions in the Nucleus Tractus Solitarii of Chronically Hypoxic Rats. Am J Physiol Regul Integr Comp Physiol 301(2):R343-50. (Targeting Trends 11q3)

See also: Society for Neuroscience 2011 Abstracts


Carstens EE, Carstens MI, Simons CT, Jinks SL (2010) Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303-308. (Targeting Trends 10q2)

Zipancic I, Calcagnotto ME, Piquer-Gil M, Mello LE, Alvarez-Dolado M (2010) Transplant of GABAergic precursors restores hippocampal inhibitory function in a mouse model of seizure susceptibility. Cell Transplant 19(5):549-564. (Targeting Trends 10q2)

See also: Society for Neuroscience 2010 Abstracts


Nayate A, Moore SA, Weiss R, Taktakishvili OM, Lin LH, Talman WT (2009) Cardiac damage after lesions of the nucleus tractus solitarii. Am J Physiol Regul Integr Comp Physiol 296:R272-279. (Targeting Trends 09q2)

Ray AP, Chebolu S, Ramirez J, Darmani NA (2009) Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting. Behav Neurosci 123:701-706. (Targeting Trends 09q3)

Truitt WA, Johnson PL, Dietrich AD, Fitz SD, Shekhar A (2009) Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala. Neuroscience 160:284-294. (Targeting Trends 09q2)

Young B, Coolen L, McKenna K (2009) Neural regulation of ejaculation. J Sex Med 6 Suppl 3:229-233. (Targeting Trends 09q2)

Zhu J, Xu W, Wang J, Ali SF, Angulo JA (2009) The Neurokinin-1 Receptor Modulates the Methamphetamine-Induced Striatal Apoptosis and Nitric Oxide Formation in Mice. J Neurochem 111(3):656-668. (Targeting Trends 09q4)

See also: Society for Neuroscience 2009 Abstracts


Darmani NA, Wang Y, Abad J, Ray AP, Thrush GR, Ramirez J (2008) Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists. Brain Res 1214:58-72. (Targeting Trends 10q3)

Nayate A, Moore SA, Weiss RM, Taktakishvili O, Lin LH, Talman WT (2008) Cardiac Damage after Lesions of the Nucleus Tractus Solitarii. Am J Physiol Regul Integr Comp Physiol 296(2):R272-R279. (Targeting Trends 09q1)

Takakura AC, Moreira TS, Stornetta RL, West GH, Gwilt JM, Guyenet PG (2008) Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apneic threshold in rats. J Physiol 586:2975-2991. (Targeting Trends 08q3)

Wiley RG (2008) Substance P receptor-expressing dorsal horn neurons: Lessons from the targeted cytotoxin, substance P-saporin. Pain 136:7-10. (Targeting Trends 08q3)

See also: Society for Neuroscience 2008 Abstracts


Truitt WA, Sajdyk TJ, Dietrich AD, Oberlin B, McDougle CJ, Shekhar A (2007) From anxiety to autism: spectrum of abnormal social behaviors modeled by progressive disruption of inhibitory neuronal function in the basolateral amygdala in Wistar rats. Psychopharmacology (Berl) 191(1):107-118. (Targeting Trends 07q2)

Wiley RG, Kline RHt, Vierck CJ, Jr. (2007) Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar(9),Met(O(2))(11)]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 146:1333-1345. (Targeting Trends 07q3)

See also: Society for Neuroscience 2007 Abstracts


Nattie E, Li A (2006) Neurokinin-1 receptor expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat. J Appl Physiol 101(6):1596-1606. (Targeting Trends 06q4)

Wiley RG. (2006) Targeted Toxins in Pain. Targeting Trends 7(2).

See also: Society for Neuroscience 2006 Abstracts


Lappi DA (2005) Targeted Toxins from Here to There. Targeting Trends 6(3):1, 6.

Seki S, Erickson KA, Seki M, Nishizawa O, Igawa Y, Ogawa T, de Groat WC, Chancellor MB, Yoshimura N (2005) Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation. Am J Physiol Renal Physiol 288(3):F466-F473. (Targeting Trends 05q2)

See also: Society for Neuroscience 2005 Abstracts


Yezierski RP, Yu CG, Mantyh PW, Vierck CJ, Lappi DA (2004) Spinal neurons involved in the generation of at-level pain following spinal injury in the rat. Neurosci Lett 361(1-3):232-236. (Targeting Trends 04q3)

See also: Society for Neuroscience 2004 Abstracts


Stornetta RL, Rosin DL, Wang H, Sevigny CP, Weston MC, Guyenet PG (2003) A group of glutaminergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Bštzinger complex. J Comp Neurol 455(4):499-512. (Targeting Trends 03q2)

Truitt W. (2003) Deep Lumbar Neurons Control Ejaculation. Targeting Trends 4(1).

See also: Society for Neuroscience 2003 Abstracts


Truitt WA, Coolen LM (2002) Identification of a potential ejaculation generator in the spinal cord. Science 297(5586):1566-1569. (Targeting Trends 02q4)

Wang H, Germanson TP, Guyenet PG (2002) Depressor and tachypneic responses to chemical stimulation of the ventral respiratory group are reduced by ablation of neurokinin-1 receptor-expressing neurons. J Neurosci 22(9): 3755-3764. (Targeting Trends 02q3)

See also: IASP 2002 Abstracts and Society for Neuroscience 2002 Abstracts


Martin JL, Sloviter RS (2001) Focal Inhibitory Interneuron Loss and Principal Cell Hyperexcitability in the Rat Hippocampus After Microinjection of a Neurotoxic Conjugate of Saporin and a Peptidase-Resistant Analog of Substance P. Journal Comp Neurol 436:127-152. (Targeting Trends 01q4)

Sloviter R. (2001) Immunolesioning Hippocampal Inhibitory Interneurons. Targeting Trends 2(4).

See also: Society for Neuroscience 2001 Abstracts


Hunt SP, Mantyh PW (2001) The molecular dynamics of pain control. Nature Rev/Neurosci 2:83-91. (Targeting Trends 01q2)

See also: Society for Neuroscience 2000 Abstracts


Wiley RG, Lappi DA (1999) Targeting neurokinin-1 receptor-expressing neurons with [Sar9, Met(O2)11] substance P-saporin. Neurosci Lett 277(1):1-4.