Differences in carbachol dose, pain condition, and sex following lateral hypothalamic stimulation.
Lateral hypothalamic (LH) stimulation produces antinociception in female rats in acute, nociceptive pain. Whether this effect occurs in neuropathic pain or whether male-female sex differences exist is unknown. We examined the effect of LH stimulation in male and female rats using conditions of nociceptive and neuropathic pain. Neuropathic groups received chronic constriction injury (CCI) to induce thermal hyperalgesia, a sign of neuropathic pain. Nociceptive rats were naive for CCI, but received the same thermal stimulus following LH stimulation. To demonstrate that CCI ligation produced thermal hyperalgesia, males and females received either ligation or sham surgery for control. Both males and females demonstrated significant thermal hyperalgesia following CCI ligation (p<0.05), but male sham surgery rats also showed a significant left-right difference not present in female sham rats. In the second experiment, rats randomly assigned to CCI or nociceptive groups were given one of three doses of the cholinergic agonist carbachol (125, 250, or 500 nmol) or normal saline for control, microinjected into the left LH. Paw withdrawal from a thermal stimulus (paw withdrawal latency; PWL) was measured every 5 min for 45 min. Linear mixed models analysis showed that males and females in both pain conditions demonstrated significant antinociception, with the 500-nmol dose producing the greatest effect across groups compared with controls for the left paw (p<0.05). Female CCI rats showed equivalent responses to the three doses, while male CCI rats showed more variability for dose. However, nociceptive females responded only to the 500-nmol dose, while nociceptive males responded to all doses (p<0.05). For right PWL, only nociceptive males showed a significant carbachol dose response. These findings are suggestive that LH stimulation produces antinociception in male and female rats in both nociceptive and neuropathic pain, but dose response differences exist based on sex and pain condition.
The University of Michigan School of Nursing, 400 N. Ingalls Building, Ann Arbor, MI 48109-5482, United States; College of Nursing Science, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: holdenje@umich.edu.
J E
JE
Holden
University of Illinois at Chicago, College of Applied Health Sciences, 1919 W. Taylor Street, Chicago, IL 60612, United States. Electronic address: chewang@uic.edu.
E
E
Wang
Calvin College Nursing Department, Science Building Room 245, 1734 Knollcrest Circle SE, Grand Rapids, MI, United States. Electronic address: jrm3@calvin.edu.
J R
JR
Moes
The University of Michigan School of Nursing, 400 N. Ingalls Building, Ann Arbor, MI 48109-5482, United States. Electronic address: mawag@umich.edu.
M
M
Wagner
The University of Michigan School of Nursing, 400 N. Ingalls Building, Ann Arbor, MI 48109-5482, United States. Electronic address: amaduko@umich.edu.
A
A
Maduko
College of Nursing Science, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: yjeong2@khu.ac.kr.
Y
Y
Jeong
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology; D059226:Nociceptive Pain / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D018712:Analgesics, Non-Narcotic; D018679:Cholinergic Agonists; D002217:Carbachol
analgesia; antinociception; lateral hypothalamus; nociception; sex differences