How to Become Smarter (70 page)

Pain-reducing effects of cooling
(L
AY
L
ANGUAGE
S
UMMARY
): Local application of cooling (for example, to a bruise) is a well-known pain-reducing treatment. Whole-body cooling is a less obvious approach and may be more effective because it recruits different biological mechanisms. An increased level of beta-endorphin (a natural pain-killer) in blood is one such mechanism. Whole-body cooling also activates other proteins with pain-reducing properties in the spinal cord and in the brain. Both local and whole-body cooling reduce pain according to the “gate control theory of pain.” This theory states that pain signals are blocked in the spinal cord and thus do not reach the brain if certain senses are stimulated in the same body part that produces pain. For example, a person can reduce pain in the hand by applying heat, cold, or vibration to this hand. Whole-body cooling also provides psychological distraction from pain. Finally, cooling can slow down the transmission of signals by certain nerves that conduct pain.

Local application of cold is a fairly well known analgesic modality [
411
,
413
,
414
,
732
], and we will not discuss it at length. There is an excellent review of this topic in an article by Nadler
et al
. [
412
]. A less obvious approach is systemic cooling, which has an analgesic effect according to numerous animal studies [
733
-
738
] as well as several studies with human subjects [
365
,
388
,
739
]. Systemic cooling most likely causes antinociception through mechanisms different from those of local cooling, although there are some shared mechanisms too, as discussed later. Several clinical trials have tested whole-body cryotherapy (by means of cold air) in patients with rheumatoid arthritis, osteoarthritis, and fibromyalgia. Whole-body cryotherapy reduced pain for 1.5-2 hours and also reduced inflammation (if it was present) in a more sustained manner [
388
,
739
,
740
]. The winter swimming studies, which we discussed in the main text, reported that patients with asthma and rheumatoid arthritis experienced reduction of pain as a result of immersion in ice-cold water four times a week [
365
]. Additionally, numerous experiments on laboratory animals in the last 3 decades have shown that a brief cold-water swim causes substantial antinociception [
733
,
734
,
736
-
738
]. This analgesia lasts for 5-15 minutes in experiments with phasic pain [
742
-
744
] and for 1-1.5 hours after the procedure in experiments involving tonic pain [
388
,
738
,
745
].

Animal studies suggest that there are several possible mechanisms of cold swim-induced analgesia. This effect may have something to do with a sharp increase in the plasma level of beta-endorphin after exposure to cold [
746
-
751
]. Beta-endorphin is an opioid peptide with analgesic properties [
747
] and it is secreted by the pituitary gland. Its secretion correlates with activation of the hypothalamic-pituitary-adrenal axis, in particular, this peptide is produced from the same precursor protein as adrenocorticotropic hormone [
746
]. Exposure to cold activates the hypothalamic-pituitary-adrenal axis [
752
,
753
], and this may explain the transient increase of plasma beta-endorphin level following systemic cooling. Opioid peptides such as beta-endorphin can bind to opioid receptors located on nerve terminals both presynaptically and postsynaptically and thereby affect excitability of neurons participating in nociception [
754
]. Plasma beta-endorphin exerts its action peripherally [
734
,
743
,
755
]. In addition, there are
central
opioid-mediated mechanisms of cold swim-induced analgesia [
737
,
742
,
756
,
757
]. Research shows that these mechanisms involve enkephalins (another group of opioid peptides) and delta
₁
- and delta
₂
-opioid receptors located in the brain and descending pathways in the spinal cord [
737
,
742
,
757
]. Another mechanism of cold swim-induced antinociception is non-opioid in nature and is mediated by locus ceruleus in the brain and noradrenergic pathways in the spinal cord [
758
-
760
]. Although the non-opioid component of cold-swim analgesia diminishes with repeated cold swims [
733
,
736
], the central opioid component is enhanced in laboratory animals [
736
,
756
].

An additional mechanism of antinociception that may apply to both local and systemic cooling is the gate control effect of sensory stimulation [
412
]. The gate control theory of pain appeared in the 1960s and it suggests that a person can relieve local pain by stimulating sensory receptors in the same body part through immersion in hot water, vibration, and so on [
729
]. Laminae in the dorsal horn of the spinal cord transmit both pain-related and tactile signals [
412
,
729
]. Activation of local tactile receptors can “close the gate for pain,” i.e. it can suppress transmission of impulses from local pain fibers [
412
,
729
]. Some studies suggest that a similar gate control effect may also take place in a brain region called periaqueductal grey matter [
761
]. Using the example of the head shower from the
seventh section
of Chapter Two, application of cold water to the head will provide sensory stimulation to the trigeminovascular system and thereby may desensitize this system and increase the threshold of pain. The trigeminal nerve, which innervates the face and most of the scalp, plays an important role in the pathophysiology of many headache disorders. Nociceptors of the trigeminovascular system in the meninges are primarily responsible for the painful sensation of headache [
762
]. Several studies have shown that head cooling is indeed effective against headache [
411
-
414
].

A related mechanism of cooling-induced analgesia may be the psychological distraction from pain that the systemic cooling provides [
761
]. It is noteworthy that distraction from pain is among the main objectives of psychosocial interventions for patients with pain [
763
]. Finally, cooling of tissue also reduces conductivity of nociceptors, the phenomenon known as cold-induced neuropraxia [
412
], which can contribute to the analgesia associated with exposure to cold.

Antinausea effect of cooling
(L
AY
L
ANGUAGE
S
UMMARY
): Brief exposure to cold can improve bad appetite and continuous exposure to cold increases normal appetite and causes a weight loss in laboratory animals. This effect on appetite may be the result of the reduced activity of serotonin in the brain and the changes in the blood level of some hormones (leptin, thyroid hormones and ACTH).

Both chronic and intermittent exposure to cold increase food intake in homeothermic animals, which is related to increased energy expenditure (upregulation of heat production in order to maintain normal body temperature) [
368
,
395
,
764
,
765
]. For example, food consumption increases in dairy and beef cattle when they stay in unheated housing during the cold time of the year [
764
]. In an experiment by Bing
et al
. [
765
], the researchers placed rats in a cold environment (4°C) for three weeks and this resulted in a 10% increase of food intake in cold-exposed rats compared to controls. Chambers
et al.
[
368
] reported similar results in rats after one week of chronic cold exposure. Food intake quickly returned to baseline after the rats returned to a thermoneutral environment [
368
,
765
]. In another study, Holloszy and Smith [
395
] kept rats immersed in cold water (23°C) for 4 hours 5 days per week, and this regimen resulted in a 44% increase of food intake and also increased average metabolic rate. Paradoxically, body weight of cold-exposed animals always declined in the above experiments, despite increased food consumption [
368
,
395
,
765
]. For example, Bing and colleagues observed a 14% weight loss in the cold-exposed rats after 3 weeks [
765
]. The weight loss is due to the increased energy expenditure and less efficient nutrient assimilation during exposure to cold [
764
,
766
]. The effects of
brief
repeated exposure to cold on weight may be different. Two studies in Czech Republic have shown that relatively brief immersion in cold water several times a week for 4 to 6 weeks results in a slight (statistically insignificant) increase of body fat in human subjects, although these authors did not measure changes in food intake [
386
,
767
]. It is possible that the slight weight gain rather than weight loss happens with brief repeated exposure to cold because this approach does not increase metabolic rate but produces neurohormonal changes that will stimulate appetite. Possible mechanisms behind the increased food intake during exposure to cold may be the following:

1. Exposure to cold inhibits production of leptin (a peptide hormone) by adipose tissue and this causes a drop of plasma concentration of leptin [
   765
   ,
   768
   ]. This in turn leads to diminished inhibitory action of leptin on the “appetite center” in the hypothalamus [
   769
   ]. Since leptin is a known negative regulator of appetite [
   770
   ], the lowered plasma level of leptin can explain stimulation of appetite during exposure to cold.
   
2. Exposure to cold causes transient activation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes and the resultant increase in the plasma levels of adrenocorticotropic hormone (ACTH) [
   771
   -
   773
   ], triiodothyronine [
   702
   -
   704
   ], and thyroxine [
   702
   ,
   704
   ]. The cold-induced improvement of appetite may have to do with these hormones because injections of the thyroid hormones increase food intake in laboratory animals [
   704
   ,
   774
   -
   776
   ] and intravenous ACTH injections reduce nausea in human subjects [
   777
   -
   781
   ]. On the other hand, some reports have shown no change in thyroid hormones in human subjects after 1-hour exposure to cold, despite increased metabolic rate [
   731
   ]. It is possible that the effect of cooling on thyroid hormones in humans is small and transient and the plasma concentrations return to baseline within 1 hour [
   701
   ].
   
3. Exposure to cold reduces the level of serotonin in most regions of the brain [
   679
   ,
   680
   ], which, theoretically, may increase appetite (or attenuate reduction of appetite) because cerebral serotonergic circuits participate in the induction of nausea [
   782
   ,
   783
   ] and negative regulation of appetite [
   784
   ]. For example, the serotonin-releasing agent d-fenfluramine quickly elevates the extracellular level of serotonin in the brain and suppresses appetite [
   784
   ].