SP-SAP References

Cat #IT-07


Noe C, McDermott E. (2015) SP-SAP Human Clinical Trial for Cancer Pain – An Anesthesiologist’s Point of View. Targeting Trends 16(3).

Pergolizzi JV, Gharibo C, Ho KY. (2014) Treatment Considerations for Cancer Pain: A Global Perspective. Pain Pract Epub(Targeting Trends 15q3)


Frankel AE, Nymeyer H, Lappi DA, Higgins D, Ahn C, Noe C. (2014) Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain. J Clin Oncol 32 (suppl 31):191. (Targeting Trends 15q2)


Brown DC, Agnello K. (2013) Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185. (Targeting Trends 14q1)

Hayashida K. (2013) Substance P-Saporin for Bone Cancer Pain in Dogs: Can Man’s Best Friend Solve the Lost in Translation Problem in Analgesic Development? Anesthesiology 119(5):999-1000. (Targeting Trends 14q1)

Wiese AJ, Rathbun M, Butt MT, Malkmus SA, Richter PJ, Osborn KG, Xu Q, Veesart SL, Steinauer JJ, Higgins D, Lappi DA, Russell B, Yaksh TL. (2013) Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 119(5):1163-1177. (Targeting Trends 14q1)


Man SH, Geranton SM, Hunt SP. (2012) Lamina I NK1 expressing projection neurones are functional in early postnatal rats and contribute to the setting up of adult mechanical sensory thresholds. Mol Pain 8(1):35. (Targeting Trends 12q4)


de Carvalho D, Bicego KC, de Castro OW, da Silva GS, Garcia-Cairasco N, Gargaglioni LH (2010) Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia. Respir Physiol Neurobiol 172(1-2):24-31. (Targeting Trends 10q3)


Halasz J, Zelena D, Toth M, Tulogdi A, Mikics E, Haller J (2009) Substance P neurotransmission and violent aggression: the role of tachykinin NK(1) receptors in the hypothalamic attack area. Eur J Pharmacol 611:35-43. (Targeting Trends 09q3)

Rivat C, Vera-Portocarrero LP, Ibrahim MM, Mata HP, Stagg NJ, De Felice M, Porreca F, Malan TP (2009) Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain. Eur J Neurosci 29:727-737. (Targeting Trends 09q2)


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 54:269-279. (Targeting Trends 08q2)

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. (Targeting Trends 08q3)

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. (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)

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. (Targeting Trends 08q4)


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. (Targeting Trends 08q1)

Caudle RM. (2007) Inducing Central Sensitization with a Substance P/ Cholera Toxin Conjugate. Targeting Trends 8(4).

Khan IM, Wart CV, Singletary EA, Stanislaus S, Deerinck T, Yaksh TL, Printz MP (2007) Elimination of rat spinal substance P receptor bearing neurons dissociates cardiovascular and nocifensive responses to nicotinic agonists. Neuropharmacology 54(2):269-279. (Targeting Trends 08q1)

Lappi DA (2007) Targeted Therapy for Chronic Pain. Targeting Trends 8(3):1.

Potts JT. (2007) Nucleus tractus solitarii injections of substance P-conjugated saporin selectively disrupts baroflex-dependent pathways. Targeting Trends 8(2).

Potts JT, Fong AY, Anguelov PI, Lee S, McGovern D, Grias I (2007) Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex. Neuroscience 145(3):1168-1181. (Targeting Trends 07q2)

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. (Targeting Trends 07q3)

Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F (2007) Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain 129:35-45. (Targeting Trends 07q3)

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


Abdala AP, Schoorlemmer GH, Colombari E (2006) Ablation of NK(1) receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats. Brain Res 1119(1):165-173. (Targeting Trends 07q1)

Allen JW. (2006) Safety and Efficacy of Substance P-SAP. Targeting Trends 7(3).

Allen JW, Mantyh PW, Horais K, Tozier N, Rogers SD, Ghilardi JR, Cizkova D, Grafe MR, Richter P, Lappi DA, Yaksh TL (2006) Safety evaluation of Intrathecal Substance P-Saporin, a targeted neurotoxin, in dogs. Toxicol Sci 91(1):286-298. (Targeting Trends 06q2)

Basbaum AI, Julius D (2006) Toward better pain control. Sci Am 294(6):60-67. (Targeting Trends 06q3)

Castro AR, Pinto M, Lima D, Tavares I (2006) Secondary hyperalgesia in the monoarthritic rat is mediated by GABA(B) and NK1 receptors of spinal dorsal horn neurons: A behavior and c-fos study. Neuroscience 141(4):2087-2095. (Targeting Trends 06q4)

Ohtori S, Inoue G, Koshi T, Ito T, Doya H, Moriya H, Takahashi K (2006) Substance P-saporin down-regulates substance P receptor immunoreactive sensory dorsal root ganglion neurons innervating the lumbar intervertebral discs in rats. Spine 31:2987-2991. (Targeting Trends 07q2)

Rygh LJ, Suzuki R, Rahman W, Wong Y, Vonsy JL, Sandhu H, Webber M, Hunt S, Dickenson AH (2006) Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci 24(3):761-772. (Targeting Trends 06q4)

Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F (2006) Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain 129(1-2):35-45. (Targeting Trends 07q1)

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

See also: Society for Neuroscience 2006 Abstracts


Abe T, Ohshita N, Sugiyo S, Moritani M, Kobayashi M, Takemura M (2005) Elimination of neurokinin-1 receptor neurons in caudal nucleus reverses the effects of systemic bicuculline on c-Fos expression in rat trigeminal sensory nucleus: I. High intensity electrical stimulation of the trigeminal ganglion. Neuroscience 133(3):739-747. (Targeting Trends 05q4)

Chiken S, Tokuno H (2005) Impairment of skilled forelimb use after ablation of striatal interneurons expressing substance P receptors in rats: an analysis using a pasta matrix reaching task. Exp Brain Res 162(4):532-536. (Targeting Trends 05q2)

Khasabov SG, Ghilardi JR, Mantyh PW, Simone DA (2005) Spinal neurons that express NK-1 receptors modulate descending controls that project through the dorsolateral funiculus. J Neurophysiol 93(2):998-1006. (Targeting Trends 05q1)

McKay LC, Janczewski WA, Feldman JL (2005) Sleep-disordered breathing after targeted ablation of preBotzinger complex neurons. Nat Neurosci 8(9):1142-1144. (Targeting Trends 06q1)

Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH (2005) Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain 117(3):292-303. (Targeting Trends 05q4)

Whiteside GT, Woods ME, Pearson MS, Pomonis JD, Turchin PI, Walker K (2005) Ablation of a population of neurons in the dorsal horn of the spinal cord is insufficient to induce sprouting of touch responsive myelinated afferents into the innervation territory of pain sensitive unmyelinated afferents. Med Hypotheses Res 2:275-282. (article)


Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV (2004) Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe-area in awake goats. J Appl Physiol 97(6):2236-2247. (Targeting Trends 05q1)(Targeting Trends 05q1)

Nattie EE, Li A, Richerson GB, Lappi DA (2004) Medullary serotonergic neurons and adjacent neurons that express neurokinin-1 receptors are both involved in chemoreception in vivo. J Physiol 556(1):235-253. (Targeting Trends 04q2)

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, Forster HV (2004) Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Botzinger complex area induces abnormal breathing periods in awake goats. J Appl Physiol 97(5):1620-1628. (Targeting Trends 05q1)

Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah TR, Davis S, Forster HV (2004) Large lesions in the pre-Botzinger complex area eliminate eupneic respiratory rhythm in awake goats. J Appl Physiol 97(5):1629-1636. (Targeting Trends 05q1)

See also: Society for Neuroscience 2004 Abstracts


Chiken S, Hatanaka N, Tokuno H (2003) Cytochrome oxidase activity in the monkey globus pallidus and subthalamic nucleus after ablation of striatal interneurons expressing substance P receptors. Neurosci Lett 353(2):103-106. (Targeting Trends 04q1)

Chiken S, Tokuno H (2003) Ablation of striatal interneurons influences activities of entopeduncular neurons. Neuroreport 14(5):675-678. (Targeting Trends 03q3)

Feldman JL, Mitchell GS, Nattie EE (2003) Breathing: Rhythmicity, Plasticity, Chemosensitivity. Annu Rev Neurosci 26:239-266. (Targeting Trends 03q3)

Gadd CA, Murtra P, De Felipe C, Hunt SP (2003) Neurokinin-1 receptor-expressing neurons in the amygdala modulate morphine reward and anxiety behaviors in the mouse. J Neurosci 23(23):8271-8280. (Targeting Trends 03q4)

Levita L, Mania I, Rainnie DG (2003) Subtypes of substance P receptor immunoreactive interneurons in the rat basolateral amygdala. Brain Res 981(1-2):41-51. (Targeting Trends 03q4)

Vierck CJ, Kline RH, Wiley RG (2003) Intrathecal substance p-saporin attenuates operant escape from nociceptive thermal stimuli. Neuroscience 119(1):223-232. (Targeting Trends 03q3)

See also: Society for Neuroscience 2003 Abstracts


Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA (2002) Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 22(20):9086-9098. (Targeting Trends 03q1)

Mantyh PW (2002) Neurobiology of substance P and the NK1 receptor. J Clin Psychiatry 63(Suppl 11):6-10. (Targeting Trends 03q2)

Nattie EE, Li A (2002) Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity. J Physiol 544(Pt 2):603-616. (Targeting Trends 03q1)

Riley J, Lin LH, Chianca DA, Talman WT (2002) Ablation of NK1 receptors in rat nucleus tractus solitarii blocks baroreflexes. Hypertension 40(6):823-826. (Targeting Trends 03q2)

Simons CT, Gogineni AG, Iodi Carstens M, Carstens E (2002) Reduced aversion to oral capsaicin following neurotoxic destruction of superficial medullary neurons expressing NK-1 receptors. Brain Res 945:139-143. (Targeting Trends 02q4)

Suzuki R, Morcuende S, Webber M, Hunt SP, Dickenson AH (2002) Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci 5(12):1319-1326.

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


Gray PA, Janczewski WA, Mellen N, McCrimmon DR, Feldman JL (2001) Normal breathing requires preBotzinger complex neurokinin-1 receptor-expressing neurons. Nat Neurosci 4(9):927-930.

Summary: SP-SAP was effective in eliminating preBötC NK1R neurons in adult rats. Unilateral SP-SAP injection transiently produced sighs (large inspiratory efforts followed by prolonged expiration).
Dose: Injections of 0.1–0.2 pmol of SP-SAP or 0.3 pmol each of unconjugated Saporin and Substance P were made in the pre-BötC.

Higgins D (2001) Safety Studies Begin for Chronic Pain Therapeutic. Targeting Trends 2(2):1, 6.

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

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

See also: Society for Neuroscience 2001 Abstracts


Friedrich, M.J. (2000) Loss of nerve: a molecular approach to better treatment of chronic pain. JAMA 283(2):187-188.  (Targeting Trends 01q1)

Hunt SP (2000) Pain control: breaking the circuit. Trends Pharmacol Sci 21:284-287. (Targeting Trends 01q1)

Wiley RG (2000) Neuropeptide-toxin conjugates in pain research and treatment. (Review) Reg Anesth Pain Med 25(5):546-548. (Targeting Trends 01q3)

Wiley RG, Kline IV RH (2000) Neuronal lesioning with axonally transported toxins. J Neurosci Methods 103:73-82. (Targeting Trends 01q2)

See also: Society for Neuroscience 2000 Abstracts


Nichols ML, Allen BJ, Rogers SD, Ghilardi JR, Honore P, Luger NM, Finke MP, Li J, Lappi DA, Simone DA, Mantyh PW (1999) Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science 286:1558-1561.


Mantyh PW, Rogers SD, Honore P, Allen BJ, Ghilardi JR, Li J, Daughters RS, Lappi DA, Wiley RG, Simone DA (1997) Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279.

Wiley RG, Lappi DA (1997) Destruction of neurokinin-1 receptor expressing cells in vitro and in vivo using substance P-saporin. Neurosci Lett 230:97-100.