title: Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat.
abstract: OBJECTIVE
  Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet.
  
  
  METHODS
  Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated.
  
  
  RESULTS
  Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision.
  
  
  CONCLUSIONS
  In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: M
authors.initials: M
authors.lastname: Gautam
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: P
authors.initials: P
authors.lastname: Prasoon
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: K H
authors.initials: KH
authors.lastname: Reeta
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Kaler
authors.affiliation: Departments of Anatomy and Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: S B
authors.initials: SB
authors.lastname: Ray
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009437:Neuralgia / Q000378:metabolism*; D059225:Nociception / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: C114226:L 760735; D009025:Morpholines; D018040:Receptors, Neurokinin-1; D013373:Substance P