SECTION VII THE NERVOUS SYSTEM Colon Cancer A 75-year-old mn developed cancer of the colon.The cancer resulted in severe pain.because of both visceral pain and metastases to bone of the vertebral column. Morphine controlled the pain initially,but eventually the pain became so severe that the required high doses of morphine interfered with the ability of the patient to think clearly.Several options were considered to improve the quality of the patient's life during his terminal period:1)installation of a patient-comtrolled epidural morphine pump:2)bilateral cordotomies:and 3)deep brain stimulation. 1.Why was morphine able to control the cancer pain initially?That is,where and how does morphine act when given systenically to control pain? 2.How would epidural infusion of morphine be able to control the pain of colon cancer?What is the advantage of alloving a patient to comtrol a morphime pump? 3.What can be done if an inadvertent overdose of morphine leads to respiratory arrest? 4.What are the advantages and disadvantages of anterolateral cordotomy? 5.What would be a suitable target for deep brain stimulation to control cancer pain? ANSVER 1.Morphine given systemically my act prinarily at the level of the periaqueductal gray in the nidbrain.This area is richly provided with opiate receptors,and microinjection of opfates here produces analgesia.The mechanisn of the opiate action may reduce the activity of inhibitory interneurons.and the reduced activity may disinhibit the descending analgesia pathways that originate in the periaqueduetal gray.These analgesia pathsays in turn inhibit nociceptive
SECTION VII THE NERVOUS SYSTEM Colon Cancer A 75-year-old man developed cancer of the colon. The cancer resulted in severe pain, because of both visceral pain and metastases to bone of the vertebral column. Morphine controlled the pain initially, but eventually the pain became so severe that the required high doses of morphine interfered with the ability of the patient to think clearly. Several options were considered to improve the quality of the patient's life during his terminal period: 1) installation of a patient-controlled epidural morphine pump; 2) bilateral cordotomies; and 3) deep brain stimulation. 1. Why was morphine able to control the cancer pain initially? That is, where and how does morphine act when given systemically to control pain? 2. How would epidural infusion of morphine be able to control the pain of colon cancer? What is the advantage of allowing a patient to control a morphine pump? 3. What can be done if an inadvertent overdose of morphine leads to respiratory arrest? 4. What are the advantages and disadvantages of anterolateral cordotomy? 5. What would be a suitable target for deep brain stimulation to control cancer pain? ANSWER 1. Morphine given systemically may act primarily at the level of the periaqueductal gray in the midbrain. This area is richly provided with opiate receptors, and microinjection of opiates here produces analgesia. The mechanism of the opiate action may reduce the activity of inhibitory interneurons, and the reduced activity may disinhibit the descending analgesia pathways that originate in the periaqueductal gray. These analgesia pathways in turn inhibit nociceptive
transnission (e.g.,by inhibiting spinothalanic tract neuroms)in the spinal cord dorsal horn. 2 Opiate receptors also occur in the spinal cord dorsal horn.For effective activation.these receptors require a higher dose of systenic morphine than do those in the periaqueductal gray.However,they can be directly activated if morphine is applied to the spinal cord.This can be done by epidural injection.Oorphine readily penetrates the dura because of its solubility in lipid memhranes.Thus epidural infusion of morphine can be used to block nociceptive transmission at the spinal cord level.Patient-controlled analgesia is beccming a widely accepted technique. In the usual hospital setting,morphine doses are given too infrequently to allow the plassa concentration to remain at a stable level.Thus the plasma concentration swings between a level that is insufficient for analgesia and one that causes somnolence.With patient control,the morphine level is kept optiml for analgesia. Interestingly,the total dose is less than that usually given with the alternative reginen. 3.Respiratory depression is a potential complication of a rorphine overdose. whether the porphine is given systemically or by epidural pump.The opiate receptor antagonist.naloxome,can be used to counteract the action of morphine. 4.Anterolateral cordotory used to be the procedure of choice to control cancer pain.especially when the cancer was at a low segmental level.However,the original open procedure required surgical exposure of the spinal cord.More recently. percutaneous cordotom has become feasible,so that lesions are made by inserting a needle through the intervertebral foranen between Cl and C2.This can be done in conscious patiemts.However,destructive procedures are now generally thought to be less desirable tham the use of analgesics to control pain.In the case of pelvie cancer pain.there is the further disadvantage that the pain originates bilaterally: therefore a bilateral cordotomy would likely be required.Bilateral percutaneous cordotomies run the risk of interrupting the descending respiratory control pathways
transmission (e.g., by inhibiting spinothalamic tract neurons) in the spinal cord dorsal horn. 2. Opiate receptors also occur in the spinal cord dorsal horn. For effective activation, these receptors require a higher dose of systemic morphine than do those in the periaqueductal gray. However, they can be directly activated if morphine is applied to the spinal cord. This can be done by epidural injection. (Morphine readily penetrates the dura because of its solubility in lipid membranes.) Thus epidural infusion of morphine can be used to block nociceptive transmission at the spinal cord level. Patient-controlled analgesia is becoming a widely accepted technique. In the usual hospital setting, morphine doses are given too infrequently to allow the plasma concentration to remain at a stable level. Thus the plasma concentration swings between a level that is insufficient for analgesia and one that causes somnolence. With patient control, the morphine level is kept optimal for analgesia. Interestingly, the total dose is less than that usually given with the alternative regimen. 3. Respiratory depression is a potential complication of a morphine overdose, whether the morphine is given systemically or by epidural pump. The opiate receptor antagonist, naloxone, can be used to counteract the action of morphine. 4. Anterolateral cordotomy used to be the procedure of choice to control cancer pain, especially when the cancer was at a low segmental level. However, the original open procedure required surgical exposure of the spinal cord. More recently, percutaneous cordotomy has become feasible, so that lesions are made by inserting a needle through the intervertebral foramen between C1 and C2. This can be done in conscious patients. However, destructive procedures are now generally thought to be less desirable than the use of analgesics to control pain. In the case of pelvic cancer pain, there is the further disadvantage that the pain originates bilaterally; therefore a bilateral cordotomy would likely be required. Bilateral percutaneous cordotomies run the risk of interrupting the descending respiratory control pathways
5.Deep brain stimulation is an experinental procedure that is not used in ordinary practice.When it has been used experimentally to control cancer pain that results fron the activation of peripheral nociceptors,the main target has been the periventricular gray (ust rostral to the periaqueductal gray).Stisulation in the periaqueductal gray has the disadvantage that eye movenents generally result.In addition,stimulation in this area can evoke a sensation of fear.The effectiveness of periventricular gray stirulation is controversial
5. Deep brain stimulation is an experimental procedure that is not used in ordinary practice. When it has been used experimentally to control cancer pain that results from the activation of peripheral nociceptors, the main target has been the periventricular gray (just rostral to the periaqueductal gray). Stimulation in the periaqueductal gray has the disadvantage that eye movements generally result. In addition, stimulation in this area can evoke a sensation of fear. The effectiveness of periventricular gray stimulation is controversial