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The anterior cingulate cortex and pain processing.

Fuchs PN, Peng YB, Boyette-Davis JA, Uhelski ML - Front Integr Neurosci (2014)

Bottom Line: Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain.The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus.These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Texas at Arlington, Arlington TX, USA ; Department of Biology, University of Texas at Arlington, Arlington TX, USA.

ABSTRACT
The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents.

No MeSH data available.


Related in: MedlinePlus

Systemic Morphine. (A) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. (B) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline at that time point; ** p < 0.01 versus Ligation/saline at that time point; *** p < 0.001 versus Ligation/saline at that time point; ###p < 0.001 versus same group at pre-injection time point. (C) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. (D) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline; ** p < 0.01 versus Ligation/saline; *** p < 0.001 versus Ligation/saline (Reprint from LaGraize et al., 2006).
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Figure 5: Systemic Morphine. (A) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. (B) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline at that time point; ** p < 0.01 versus Ligation/saline at that time point; *** p < 0.001 versus Ligation/saline at that time point; ###p < 0.001 versus same group at pre-injection time point. (C) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. (D) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline; ** p < 0.01 versus Ligation/saline; *** p < 0.001 versus Ligation/saline (Reprint from LaGraize et al., 2006).

Mentions: This work suggests that one possible mechanism of action by which the ACC selectively modulates pain affect is via the mu-opioid receptor system. This idea is based on the evidence that the ACC has a high density of opioid receptors (Lewis et al., 1983; Mansour et al., 1987; Kujirai et al., 1991; Vogt et al., 1995), and that activation of the ACC mu-opioid receptor system during sustained pain is negatively correlated with McGill Pain Questionnaire affective scores (Zubieta et al., 2001) and the Positive and Negative Affectivity Scale (Zubieta et al., 2003). In a more recent study, we tested the functional role of the ACC opiate system in the selective modulation of pain affect in an animal model of neuropathic pain utilizing the methods of mechanical paw withdrawal threshold and escape/avoidance behavior testing (LaGraize et al., 2006). Systemic administration of low dose morphine produced a selective attenuation of pain affect, as indicated by a decrease in the amount of time that animals spent in the light side of the chamber in nerve damaged animals, with no alteration of mechanical paw withdrawal threshold (Figure 5). Supraspinally, morphine microinjection into the ACC again produced a selective decrease in escape/avoidance to mechanical stimulation of the hyperalgesic paw with no change of mechanical paw withdrawal threshold. Since the ACC has been implicated in learning and memory processes (Peretz, 1960; Kimble and Gostnell, 1968; Seamans et al., 1995; Engström et al., 2013), it is possible that morphine administration interferes with the acquisition and retention of information in the PEAP rather than decreasing the negative hedonic value of the mechanical stimulus. Impaired performance following morphine administration has been reported in tests of spatial memory in the Morris water maze (McNamara and Skelton, 1992) and the radial arm maze (Spain and Newsom, 1991). However, it should be noted that the effect of morphine on the radial arm maze requires chronic high dose administration (up to 40 mg/kg) that is most likely associated with sedation and impairment in task performance rather than with interference of working memory (Spain and Newsom, 1991). Other investigators report biphasic results in rats such that lower doses of morphine enhance while higher doses impair memory (Ageel et al., 1976; Galizio et al., 1994). Avoidance responding has been reported to be unaltered following morphine administration at doses that inhibit reflexive withdrawal responding in non-human primates (Yeomans et al., 1995). Further, impairment of learning and memory function is typically associated with manipulations to the more posterior regions of the cingulate cortex. It is therefore unlikely that our results can be explained as a failure to learn, however ongoing research is comparing the role of the anterior versus the posterior cingulate cortex on spatial learning and pain processing.


The anterior cingulate cortex and pain processing.

Fuchs PN, Peng YB, Boyette-Davis JA, Uhelski ML - Front Integr Neurosci (2014)

Systemic Morphine. (A) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. (B) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline at that time point; ** p < 0.01 versus Ligation/saline at that time point; *** p < 0.001 versus Ligation/saline at that time point; ###p < 0.001 versus same group at pre-injection time point. (C) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. (D) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline; ** p < 0.01 versus Ligation/saline; *** p < 0.001 versus Ligation/saline (Reprint from LaGraize et al., 2006).
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Figure 5: Systemic Morphine. (A) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. (B) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following drug administration (Saline, 0.5 mg/kg morphine, 1.0 mg/kg morphine) for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline at that time point; ** p < 0.01 versus Ligation/saline at that time point; *** p < 0.001 versus Ligation/saline at that time point; ###p < 0.001 versus same group at pre-injection time point. (C) Mean ± SEM mechanical paw withdrawal threshold difference scores (left paw–right paw) prior to and following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. (D) Mean ± SEM percentage of time within the light side of the test chamber for the duration of the 30-min test period following microinjection (Saline, 20 µg/µl morphine) into the ACC for animals with sham ligation or ligation of the L5 spinal nerve. * p < 0.05 versus Ligation/saline; ** p < 0.01 versus Ligation/saline; *** p < 0.001 versus Ligation/saline (Reprint from LaGraize et al., 2006).
Mentions: This work suggests that one possible mechanism of action by which the ACC selectively modulates pain affect is via the mu-opioid receptor system. This idea is based on the evidence that the ACC has a high density of opioid receptors (Lewis et al., 1983; Mansour et al., 1987; Kujirai et al., 1991; Vogt et al., 1995), and that activation of the ACC mu-opioid receptor system during sustained pain is negatively correlated with McGill Pain Questionnaire affective scores (Zubieta et al., 2001) and the Positive and Negative Affectivity Scale (Zubieta et al., 2003). In a more recent study, we tested the functional role of the ACC opiate system in the selective modulation of pain affect in an animal model of neuropathic pain utilizing the methods of mechanical paw withdrawal threshold and escape/avoidance behavior testing (LaGraize et al., 2006). Systemic administration of low dose morphine produced a selective attenuation of pain affect, as indicated by a decrease in the amount of time that animals spent in the light side of the chamber in nerve damaged animals, with no alteration of mechanical paw withdrawal threshold (Figure 5). Supraspinally, morphine microinjection into the ACC again produced a selective decrease in escape/avoidance to mechanical stimulation of the hyperalgesic paw with no change of mechanical paw withdrawal threshold. Since the ACC has been implicated in learning and memory processes (Peretz, 1960; Kimble and Gostnell, 1968; Seamans et al., 1995; Engström et al., 2013), it is possible that morphine administration interferes with the acquisition and retention of information in the PEAP rather than decreasing the negative hedonic value of the mechanical stimulus. Impaired performance following morphine administration has been reported in tests of spatial memory in the Morris water maze (McNamara and Skelton, 1992) and the radial arm maze (Spain and Newsom, 1991). However, it should be noted that the effect of morphine on the radial arm maze requires chronic high dose administration (up to 40 mg/kg) that is most likely associated with sedation and impairment in task performance rather than with interference of working memory (Spain and Newsom, 1991). Other investigators report biphasic results in rats such that lower doses of morphine enhance while higher doses impair memory (Ageel et al., 1976; Galizio et al., 1994). Avoidance responding has been reported to be unaltered following morphine administration at doses that inhibit reflexive withdrawal responding in non-human primates (Yeomans et al., 1995). Further, impairment of learning and memory function is typically associated with manipulations to the more posterior regions of the cingulate cortex. It is therefore unlikely that our results can be explained as a failure to learn, however ongoing research is comparing the role of the anterior versus the posterior cingulate cortex on spatial learning and pain processing.

Bottom Line: Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain.The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus.These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Texas at Arlington, Arlington TX, USA ; Department of Biology, University of Texas at Arlington, Arlington TX, USA.

ABSTRACT
The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents.

No MeSH data available.


Related in: MedlinePlus